Eco-friendly green approach of nickel oxide
nanoparticles for biomedical applications

Suresh Sagadevan, Is Fatimah, Jayasingh Anita Lett, Md Zillur Rahman,

Won-Chun Oh, Estelle Léonard

► To cite this version:

Suresh Sagadevan, Is Fatimah, Jayasingh Anita Lett, Md Zillur Rahman, Won-Chun Oh, et al.. Eco-friendly green approach of nickel oxide nanoparticles for biomedical applications. Open Chemistry, 2023, 21 (1), 10.1515/chem-2023-0141. [hal-04390009](https://hal.science/hal-04390009)

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# Eco-friendly green approach of nickel oxide nanoparticles for biomedical applications

Suresh Sagadevan, Is Fatimah, Jayasingh Anita Lett, Md Zillur Rahman,

Won-Chun Oh, Estelle Léonard

► To cite this version:

Suresh Sagadevan, Is Fatimah, Jayasingh Anita Lett, Md Zillur Rahman, Won-Chun Oh, et al.. Eco-friendly green approach of nickel oxide nanoparticles for biomedical applications. Open Chemistry, 2023, 21 (1), 10.1515/chem-2023-0141. [hal-04390009]

HAL Id: hal-04390009

https://hal.science/hal-04390009v1

Submitted on 5 Jun 2024

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.
Review Article

Suresh Sagadevan*, Is Fatimah, Jayasingh Anita Lett, Md Zillur Rahman, Estelle Leonard, Won-Chun Oh*

Eco-friendly green approach of nickel oxide
nanoparticles for biomedical applications

https://doi.org/10.1515/chem-2023-0141

received July 31, 2023; accepted September 26, 2023

**Abstract:** The two most prominent areas of nanotechnology and nanoscience are environmental remediation and biomedical applications, which has a strong need to develop cleaner and more eco-friendly methods for preparing functional nanomaterials. This involves incorporating non-toxic chemicals and reagents for converting metal cations into metal or metal oxide nanoparticles (NPs), using readily available plant reagents and microbes as redox mediators. The extracts of these plants and microbes contain varying amounts of phytochemicals and metabolites that act as redox mediators and capping agents to stabilize biosynthesized NPs. Considering these natural reagents for forming metal/metal oxide NPs, the present work aims to provide a complete review of the green fabrication of nickel oxide (NiO) NPs using extracts from various plant and microbial sources. In addition, the performance of various biosynthesized NiO NPs and their potential uses in biological applications are discussed.

**Keywords:** nickel oxide nanoparticles, green synthesis, bio-medical applications

**1 Introduction**

Nanotechnology has enabled scientists to develop advanced materials with various nanoscale morphologies, including nanomaterials with unprecedented physical, chemical, and optical properties in the size range of 1–100 nm [1]. Nanomaterials produced by various conventional processes have many advantages and disadvantages, depending on the application in which they are employed [2–4]. The mechanical and chemical synthesis of nanomaterials is typically costly, labor-intensive, and potentially hazardous to the natural environment [5]. In addition, conventional chemical techniques rely largely on specialized lab-scale reactors and may produce toxins that pose significant health and safety issues to humans, ecosystems, and the environment [6]. From this perspective, green synthesis techniques are attracting the attention of researchers to produce safer materials, and many small production units have recently increased their investments in sustainable technologies [7–11]. Nanomaterials mainly produced by chemical and physical processes are used in many areas today. In addition to their inexpensive and modern synthesis methods, it is necessary to have more environmentally friendly substances (such as natural solvents, non-toxic reducing agents, and stabilizers) so that their applications can be expanded to the life science and healthcare sectors [12,13]. Therefore, research organizations are interested in developing cost-effective and environmentally benign nanoparticle (NP) synthesis processes that decrease or avoid hazardous chemicals to prevent the production of redundant and hazardous byproducts.

In general, the synthesis methods for forming NPs are divided into three categories: chemical, physical, and biological. Chemical and physical approaches are usually costly, time-consuming, and impact the environment, whereas biological methods are non-toxic, environmentally friendly, have control over size and shape, at mild reaction conditions, reduce agglomeration, and serve as cheaper alternatives for NP production [14,15]. Biological approaches can be divided into two categories: microorganism-mediated and plant extract-mediated. Plant-mediated synthesis of metal

<figure><img src="image_1.png" /></figure>

<figure><img src="image_2.png" /></figure>

<footnote>* Corresponding author: Suresh Sagadevan, Nanotechnology & Catalysis Research Centre, University of Malaya, Kuala Lumpur 50603, Malaysia; Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Islam Indonesia, Kampus Terpadu UII, Jl. Kaliurang Km 14, Sleman, Yogyakarta, Indonesia, e-mail: dsrueshnano@gmail.com</footnote>

<footnote>* Corresponding author: Won-Chun Oh, Department of Advanced Materials Science and Engineering, Hanseo University, Seosan-si, Chungnam 356-706, Korea, e-mail: wc_oh@hanseo.ac.kr</footnote>

<footnote>**Is Fatimah:** Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Islam Indonesia, Kampus Terpadu UII, Jl. Kaliurang Km 14, Sleman, Yogyakarta, Indonesia</footnote>

<footnote>**Jayasingh Anita Lett:** Department of Physics, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India</footnote>

<footnote>**Md Zillur Rahman:** Department of Mechanical Engineering, Ahsanullah University of Science and Technology, Dhaka 1208, Bangladesh</footnote>

<footnote>**Estelle Leonard:** Laboratoire TIMR UTC-ESCOM, Centre de recherche de Royallieu, rue du docteur Schweitzer, CS 60319, F-60203 Compiègne Cedex, France</footnote>
Review Article

Suresh Sagadevan*, Is Fatimah, Jayasingh Anita Lett, Md Zillur Rahman, Estelle Leonard, Won-Chun Oh*

Eco-friendly green approach of nickel oxide
nanoparticles for biomedical applications

https://doi.org/10.1515/chem-2023-0141

received July 31, 2023; accepted September 26, 2023

**Abstract:** The two most prominent areas of nanotechnology and nanoscience are environmental remediation and biomedical applications, which has a strong need to develop cleaner and more eco-friendly methods for preparing functional nanomaterials. This involves incorporating non-toxic chemicals and reagents for converting metal cations into metal or metal oxide nanoparticles (NPs), using readily available plant reagents and microbes as redox mediators. The extracts of these plants and microbes contain varying amounts of phytochemicals and metabolites that act as redox mediators and capping agents to stabilize biosynthesized NPs. Considering these natural reagents for forming metal/metal oxide NPs, the present work aims to provide a complete review of the green fabrication of nickel oxide (NiO) NPs using extracts from various plant and microbial sources. In addition, the performance of various biosynthesized NiO NPs and their potential uses in biological applications are discussed.

**Keywords:** nickel oxide nanoparticles, green synthesis, biomedical applications

**1 Introduction**

Nanotechnology has enabled scientists to develop advanced materials with various nanoscale morphologies, including nanomaterials with unprecedented physical, chemical, and optical properties in the size range of 1–100 nm [1]. Nanomaterials produced by various conventional processes have many advantages and disadvantages, depending on the application in which they are employed [2–4]. The mechanical and chemical synthesis of nanomaterials is typically costly, labor-intensive, and potentially hazardous to the natural environment [5]. In addition, conventional chemical techniques rely largely on specialized lab-scale reactors and may produce toxins that pose significant health and safety issues to humans, ecosystems, and the environment [6]. From this perspective, green synthesis techniques are attracting the attention of researchers to produce safer materials, and many small production units have recently increased their investments in sustainable technologies [7–11]. Nanomaterials mainly produced by chemical and physical processes are used in many areas today. In addition to their inexpensive and modern synthesis methods, it is necessary to have more environmentally friendly substances (such as natural solvents, non-toxic reducing agents, and stabilizers) so that their applications can be expanded to the life science and healthcare sectors [12,13]. Therefore, research organizations are interested in developing cost-effective and environmentally benign nanoparticle (NP) synthesis processes that decrease or avoid hazardous chemicals to prevent the production of redundant and hazardous byproducts.

In general, the synthesis methods for forming NPs are divided into three categories: chemical, physical, and biological. Chemical and physical approaches are usually costly, time-consuming, and impact the environment, whereas biological methods are non-toxic, environmentally friendly, have control over size and shape, at mild reaction conditions, reduce agglomeration, and serve as cheaper alternatives for NP production [14,15]. Biological approaches can be divided into two categories: microorganism-mediated and plant extract-mediated. Plant-mediated synthesis of metal

* Corresponding author: Suresh Sagadevan, Nanotechnology & Catalysis Research Centre, University of Malaya, Kuala Lumpur 50603, Malaysia; Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Islam Indonesia, Kampus Terpadu UII, Jl. Kaliurang Km 14, Sleman, Yogyakarta, Indonesia, e-mail: dsrueshnano@gmail.com

* Corresponding author: Won-Chun Oh, Department of Advanced Materials Science and Engineering, Hanseo University, Seosan-si, Chungnam 356-706, Korea, e-mail: wc_oh@hanseo.ac.kr

**Is Fatimah:** Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Islam Indonesia, Kampus Terpadu UII, Jl. Kaliurang Km 14, Sleman, Yogyakarta, Indonesia

**Jayasingh Anita Lett:** Department of Physics, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India

**Md Zillur Rahman:** Department of Mechanical Engineering, Ahsanullah University of Science and Technology, Dhaka 1208, Bangladesh

**Estelle Leonard:** Laboratoire TIMR UTC-ESCOM, Centre de recherche de Royallieu, rue du docteur Schweitzer, CS 60319, F-60203 Compiegne Cedex, France

<figure><img src="image_2.png" /></figure>

<figure><img src="image_3.png" /></figure>
NPs (MNPs) is preferred over microorganism-mediated synthesis [16]. Plant extracts contain many secondary metabolites that play essential roles in converting metal precursors into MNPs during the synthesis process [17–20]. Numerous alternative methods have been developed to synthesize biocompatible NPs, which have the benefits of avoiding chemical risks, reducing waste, and preventing pollution. Owing to the growing environmental concerns, various efforts have been made to produce NPs using plant extracts. Synthetic approaches based on naturally occurring biomaterials offer an alternative method for generating NPs, which are commonly required in the industrial sector. Green chemistry principles have motivated researchers to develop synthetic techniques, and enzymes [21], microorganisms [22], and plant extracts [23,24], all of which play an important role in the manufacturing of NPs. Compared to other biological and traditional methods, plant extract-based synthesis strategies are more environmentally friendly for alternative nanomaterial synthesis.

Among the many different kinds of MNPs, nickel oxide (NiO) is an inorganic black substance, insoluble in all solvents and susceptible to base and acid attacks [25,26]. The simplest and most practical method for obtaining NiO NPs is heating nickel(II)-based compounds, including hydroxides, nitrates, and carbonates [27,28]. High levels of Ni in soils harm plants, while the same high levels reduce algal growth in water [29]. A minimal amount of Ni must be present in animal feed; however, exceeding the recommended value can be dangerous. For example, animals living near factories are at risk of various cancer types due to nickel levels in the water and soil [30]. However, high levels of Ni at a localized level do not impact the food chain, as Ni is not accumulated in animals or plants [31]. This review article reports recent studies on NiO NPs obtained via plant- and microbe-mediated green synthesis. The biomedical applications of NiO NPs prepared using these methods are also discussed.

## 2 Green synthesis and characterization of NPs

Due to the unique characteristics of metal oxide NPs, including surface functionality and modifying capacity, small size and high reactivity, an enriched surface-area-to-volume ratio, good magnetic properties, and high biocompatibility, these NPs have gained a lot of interest. Economically viable, environmentally sustainable, and socially accessible production of NPs is highly sought after in line with a global aspiration toward green engineering solutions [32]. In recent

years, an extensive study on living organisms, such as bacteria, fungi, yeast, and plants, has used biological intermediates for the transition of inorganic metal ions into MNPs. The availability of polyphenols in naturally derived biomaterials is primarily responsible for the degradation of organic compounds using a green approach (plant extracts). Various plant extracts and their chemical constituents have been extensively studied for their utility in green synthesis, and the polyphenols present in plant extracts are responsible for certain characteristics of NPs [33–35].

### 2.1 Green synthesis

The 12 key principles of green chemistry can be used to establish green synthesis processes [36]; a common example is the biogenic production of NPs. In this approach, naturally occurring chemicals generate NPs with different characteristics. Green chemistry concepts integrate reducing hazardous reagents and increasing chemical process efficiency [37]. Compared with chemically produced NPs, NPs formed by green routes have fewer adverse effects on nature and humans. This method leads to numerous applications of NPs in various disciplines [38]. Plant extracts, plants, and microbes are examples of naturally occurring resources for biogenic synthesis, including the synthesis of metal oxide NPs [38,39]. Other biodegradable natural compounds that can be used as reagents for NP synthesis include enzymes, vitamins, and proteins. Plant extraction techniques offer advantages over others in terms of scaling up for industrial production because of their ease of use and greener processes [40]. Metal oxide NPs have emerged as next-generation, cost-effective disinfectants with enormous potential in the biomedical field, pollutant removal, and other industrial applications owing to their novel properties such as antimicrobial, photocatalytic, UV filtering, and high catalytic activity [41,42]. Figure 1 shows the green synthesis approach for forming MNPs and their applications.

### 2.2 Plant-mediated synthesis

Green synthesis has become an ideal alternative to the currently available chemical and physical synthesis methods because it is cheaper, safer, and more environmentally friendly [43–45]. During green synthesis, metal ions are reduced through putative metabolic activity, which requires relatively minimal activation energy. Much research on metal oxides has been performed using microorganisms and plants, which take
NPs (MNPs) is preferred over microorganism-mediated synthesis [16]. Plant extracts contain many secondary metabolites that play essential roles in converting metal precursors into MNPs during the synthesis process [17–20]. Numerous alternative methods have been developed to synthesize biocompatible NPs, which have the benefits of avoiding chemical risks, reducing waste, and preventing pollution. Owing to the growing environmental concerns, various efforts have been made to produce NPs using plant extracts. Synthetic approaches based on naturally occurring biomaterials offer an alternative method for generating NPs, which are commonly required in the industrial sector. Green chemistry principles have motivated researchers to develop synthetic techniques, and enzymes [21], microorganisms [22], and plant extracts [23,24], all of which play an important role in the manufacturing of NPs. Compared to other biological and traditional methods, plant extract-based synthesis strategies are more environmentally friendly for alternative nanomaterial synthesis.

Among the many different kinds of MNPs, nickel oxide (NiO) is an inorganic black substance, insoluble in all solvents and susceptible to base and acid attacks [25,26]. The simplest and most practical method for obtaining NiO NPs is heating nickel(II)-based compounds, including hydroxides, nitrates, and carbonates [27,28]. High levels of Ni in soils harm plants, while the same high levels reduce algal growth in water [29]. A minimal amount of Ni must be present in animal feed; however, exceeding the recommended value can be dangerous. For example, animals living near factories are at risk of various cancer types due to nickel levels in the water and soil [30]. However, high levels of Ni at a localized level do not impact the food chain, as Ni is not accumulated in animals or plants [31]. This review article reports recent studies on NiO NPs obtained via plant- and microbe-mediated green synthesis. The biomedical applications of NiO NPs prepared using these methods are also discussed.

## 2 Green synthesis and characterization of NPs

Due to the unique characteristics of metal oxide NPs, including surface functionality and modifying capacity, small size and high reactivity, an enriched surface-area-to-volume ratio, good magnetic properties, and high biocompatibility, these NPs have gained a lot of interest. Economically viable, environmentally sustainable, and socially accessible production of NPs is highly sought after in line with a global aspiration toward green engineering solutions [32]. In recent

years, an extensive study on living organisms, such as bacteria, fungi, yeast, and plants, has used biological intermediates for the transition of inorganic metal ions into MNPs. The availability of polyphenols in naturally derived biomaterials is primarily responsible for the degradation of organic compounds using a green approach (plant extracts). Various plant extracts and their chemical constituents have been extensively studied for their utility in green synthesis, and the polyphenols present in plant extracts are responsible for certain characteristics of NPs [33–35].

### 2.1 Green synthesis

The 12 key principles of green chemistry can be used to establish green synthesis processes [36]; a common example is the biogenic production of NPs. In this approach, naturally occurring chemicals generate NPs with different characteristics. Green chemistry concepts integrate reducing hazardous reagents and increasing chemical process efficiency [37]. Compared with chemically produced NPs, NPs formed by green routes have fewer adverse effects on nature and humans. This method leads to numerous applications of NPs in various disciplines [38]. Plant extracts, plants, and microbes are examples of naturally occurring resources for biogenic synthesis, including the synthesis of metal oxide NPs [38,39]. Other biodegradable natural compounds that can be used as reagents for NP synthesis include enzymes, vitamins, and proteins. Plant extraction techniques offer advantages over others in terms of scaling up for industrial production because of their ease of use and greener processes [40]. Metal oxide NPs have emerged as next-generation, cost-effective disinfectants with enormous potential in the biomedical field, pollutant removal, and other industrial applications owing to their novel properties such as antimicrobial, photocatalytic, UV filtering, and high catalytic activity [41,42]. Figure 1 shows the green synthesis approach for forming MNPs and their applications.

### 2.2 Plant-mediated synthesis

Green synthesis has become an ideal alternative to the currently available chemical and physical synthesis methods because it is cheaper, safer, and more environmentally friendly [43–45]. During green synthesis, metal ions are reduced through putative metabolic activity, which requires relatively minimal activation energy. Much research on metal oxides has been performed using microorganisms and plants, which take
<figure><img src="image_3.png" /><figcaption>**Figure 1:** Green synthesis and applications of MNPs.</figcaption></figure>

<figure><img src="image_4.png" /><figcaption>**Figure 2:** Schematic representation of the *Cleome simplicifolia*-mediated synthesis of NiO NPs [52].</figcaption></figure>

advantage of their ability to mediate precursor redox processes, generate metal/metal oxide NPs, and stabilize the resulting NPs [45–47]. For example, bacteria have been reported to be effectively reducing agents for metal ions, and bacterial cells are easy to culture, making them ideal for producing nanomaterials [48]. Owing to the reductive ability of its proteins and intracellular enzymes, the fungus has been used to produce NPs [49]. NPs can be synthesized on purely green principles by utilizing an eco-friendly solvent solution and stabilizing and reducing

components [50]. Chouke et al. [51] demonstrated a novel *Cleome simplicifolia*-mediated green fabrication of NiO NPs to explore *in vitro* toxicity in Bm-17 and Labeo rohita liver cells (Figure 2).

NiO nanostructures were prepared using the flower extract from *Clitoria ternatea*, as depicted in Figure 3 [52]. Additionally, the antibacterial activity of NiO NPs was tested against Gram-positive *S. aureus* and Gram-negative *E. coli*. Figure 4(a and b) displays high-resolution
<figure><img src="image_4.png" /><figcaption>**Figure 1:** Green synthesis and applications of MNPs.</figcaption></figure>

<figure><img src="image_5.png" /><figcaption>**Figure 2:** Schematic representation of the *Cleome simplicifolia*-mediated synthesis of NiO NPs [52].</figcaption></figure>

advantage of their ability to mediate precursor redox processes, generate metal/metal oxide NPs, and stabilize the resulting NPs [45–47]. For example, bacteria have been reported to be effectively reducing agents for metal ions, and bacterial cells are easy to culture, making them ideal for producing nanomaterials [48]. Owing to the reductive ability of its proteins and intracellular enzymes, the fungus has been used to produce NPs [49]. NPs can be synthesized on purely green principles by utilizing an eco-friendly solvent solution and stabilizing and reducing

components [50]. Chouke et al. [51] demonstrated a novel *Cleome simplicifolia*-mediated green fabrication of NiO NPs to explore *in vitro* toxicity in Bm-17 and Labeo rohita liver cells (Figure 2).

NiO nanostructures were prepared using the flower extract from *Clitoria ternatea*, as depicted in Figure 3 [52]. Additionally, the antibacterial activity of NiO NPs was tested against Gram-positive *S. aureus* and Gram-negative *E. coli*. Figure 4(a and b) displays high-resolution
<figure><img src="image_5.png" /><figcaption>**Figure 3:** Green synthesis of NiO nanostructures using the *Clitoria ternatea* flower extract [52].</figcaption></figure>

transmission electron microscopy (HRTEM) images of the NiO NPs at two different magnifications (100 and 10 nm). The hexagonal shape and lack of agglomeration of the NPs were observed at a magnification of 10 nm. The (2 0 0) plane of NiO was found to have a *d*-spacing of 0.218 nm

between the planes (Figure 4(c)). This result demonstrates the pristine crystalline character of the synthesized NPs. Figure 4(d) shows the diffraction rings with concentric circles.

Energy dispersive X-ray (EDX) spectroscopy is a powerful analytical technique that offers precise elemental analysis with exceptional spatial resolution. The fundamental principle of EDX spectroscopy involves directing a highly focused electron beam onto a thin sample and measuring the energy of the resulting emitted X-rays. This energy information allows for identifying atomic species present in the material under investigation. Determining elemental distributions within individual NPs is particularly valuable as it enables the characterization of their optical, catalytic, and magnetic properties [53]. The EDX elemental analysis of co-precipitated NiO indicates that the Ni content is 73.83 wt% and the O content is 12.48 wt%, as shown in Table 1 [54], and the remaining carbon comes from the acetate precursor. Zorkipli et al. [55] synthesized NiO NPs using a sol-gel approach, and the NPs were spherical and porous. Another study [56] also showed that NiO NPs synthesized by the biological method have a composition of atomic percentages as determined from the EDX spectrum (Figure 5). In particular, the composition consists of Ni (73.31%) and O (26.69%). Consequently, the atomic ratio of nickel/oxygen is 2.74. The

<figure><img src="image_6.png" /><figcaption>**Figure 4:** HRTEM images of NiO NPs at different magnifications: (a) 100 nm, (b) 10 nm, (c) 5 nm, and (d) selected area electron diffraction (SAED) pattern [52].</figcaption></figure>
<figure><img src="image_6.png" /><figcaption>**Figure 3:** Green synthesis of NiO nanostructures using the *Clitoria ternatea* flower extract [52].</figcaption></figure>

transmission electron microscopy (HRTEM) images of the NiO NPs at two different magnifications (100 and 10 nm). The hexagonal shape and lack of agglomeration of the NPs were observed at a magnification of 10 nm. The (2 0 0) plane of NiO was found to have a *d*-spacing of 0.218 nm

between the planes (Figure 4(c)). This result demonstrates the pristine crystalline character of the synthesized NPs. Figure 4(d) shows the diffraction rings with concentric circles.

Energy dispersive X-ray (EDX) spectroscopy is a powerful analytical technique that offers precise elemental analysis with exceptional spatial resolution. The fundamental principle of EDX spectroscopy involves directing a highly focused electron beam onto a thin sample and measuring the energy of the resulting emitted X-rays. This energy information allows for identifying atomic species present in the material under investigation. Determining elemental distributions within individual NPs is particularly valuable as it enables the characterization of their optical, catalytic, and magnetic properties [53]. The EDX elemental analysis of co-precipitated NiO indicates that the Ni content is 73.83 wt% and the O content is 12.48 wt%, as shown in Table 1 [54], and the remaining carbon comes from the acetate precursor. Zorkipli et al. [55] synthesized NiO NPs using a sol-gel approach, and the NPs were spherical and porous. Another study [56] also showed that NiO NPs synthesized by the biological method have a composition of atomic percentages as determined from the EDX spectrum (Figure 5). In particular, the composition consists of Ni (73.31%) and O (26.69%). Consequently, the atomic ratio of nickel/oxygen is 2.74. The

<figure><img src="image_7.png" /><figcaption>**Figure 4:** HRTEM images of NiO NPs at different magnifications: (a) 100 nm, (b) 10 nm, (c) 5 nm, and (d) selected area electron diffraction (SAED) pattern [52].</figcaption></figure>
<table><caption>**Table 1:** Elemental compositions of the synthesized NiO particles [54]</caption><thead><tr><td>Element</td><td>Weight (%)</td><td>Atom (%)</td></tr></thead><tbody><tr><td>C</td><td>13.69</td><td>35.87</td></tr><tr><td>O</td><td>12.48</td><td>24.55</td></tr><tr><td>Ni</td><td>73.83</td><td>39.58</td></tr></tbody></table>

presence of gold (Au) in the EDX spectrum may be attributed to apply a thin layer of gold to the surface of NiO NPs. This coating improves the visual clarity and overall quality of the scanning electron microscopy (SEM) images. The elevated atomic percentage ratio of Ni/O may be associated with the progression of formation during the nucleation of NiO and nickel hydroxide (Ni(OH)₂) during combustion at 600°C. Notably, when heated at 600°C for 40 min, Ni(OH)₂ undergoes full conversion to NiO within the high atomic percentage ratio of Ni/O.

Recently, researchers found that MNPs synthesized using medicinal plants have excellent anticancer effects. Indeed, green-made MNPs have received considerable attention in several medical disciplines [57,58]. Recent discoveries in phytochemicals and NPs have enabled the production of customized NPs using eco-friendly processes [59]. The production of phyto-nano-mixtures was previously achieved by adding bioactive compounds to prefabricated NPs [60], which enabled the loading of bioactive phytochemicals onto

NPs to produce functionalized NPs using a straightforward one-pot synthesis technique [61]. However, as plant extracts typically comprise a complex blend of phytochemicals such as lignans, sugars, flavonoids, polyphenols, xanthones, aromatic acids, proteins, terpenes, alkaloids, and quinones, it is difficult to identify the specific component that catalyzes the intended NP production [62]. Another issue is that climate change and location can affect phytochemical levels in plants [63]. The probable mechanism for synthesizing NiO NPs is shown in Figure 6 [64].

As a result, the properties of plant extracts are likely to vary between batches, making NP production difficult

<figure><img src="image_7.png" /><figcaption>**Figure 6:** Schematic for the step-wise synthesis of NiO NPs [64].</figcaption></figure>

<figure><img src="image_8.png" /><figcaption>**Figure 5:** EDX analysis with elemental mapping of biosynthesized NiO NPs [56].</figcaption></figure>
<table><caption>**Table 1:** Elemental compositions of the synthesized NiO particles [54]</caption><thead><tr><td>Element</td><td>Weight (%)</td><td>Atom (%)</td></tr></thead><tbody><tr><td>C</td><td>13.69</td><td>35.87</td></tr><tr><td>O</td><td>12.48</td><td>24.55</td></tr><tr><td>Ni</td><td>73.83</td><td>39.58</td></tr></tbody></table>

presence of gold (Au) in the EDX spectrum may be attributed to apply a thin layer of gold to the surface of NiO NPs. This coating improves the visual clarity and overall quality of the scanning electron microscopy (SEM) images. The elevated atomic percentage ratio of Ni/O may be associated with the progression of formation during the nucleation of NiO and nickel hydroxide (Ni(OH)₂) during combustion at 600°C. Notably, when heated at 600°C for 40 min, Ni(OH)₂ undergoes full conversion to NiO within the high atomic percentage ratio of Ni/O.

Recently, researchers found that MNPs synthesized using medicinal plants have excellent anticancer effects. Indeed, green-made MNPs have received considerable attention in several medical disciplines [57,58]. Recent discoveries in phytochemicals and NPs have enabled the production of customized NPs using eco-friendly processes [59]. The production of phyto-nano-mixtures was previously achieved by adding bioactive compounds to prefabricated NPs [60], which enabled the loading of bioactive phytochemicals onto

NPs to produce functionalized NPs using a straightforward one-pot synthesis technique [61]. However, as plant extracts typically comprise a complex blend of phytochemicals such as lignans, sugars, flavonoids, polyphenols, xanthones, aromatic acids, proteins, terpenes, alkaloids, and quinones, it is difficult to identify the specific component that catalyzes the intended NP production [62]. Another issue is that climate change and location can affect phytochemical levels in plants [63]. The probable mechanism for synthesizing NiO NPs is shown in Figure 6 [64].

As a result, the properties of plant extracts are likely to vary between batches, making NP production difficult

<figure><img src="image_8.png" /><figcaption>**Figure 6:** Schematic for the step-wise synthesis of NiO NPs [64].</figcaption></figure>

<figure><img src="image_9.png" /><figcaption>**Figure 5:** EDX analysis with elemental mapping of biosynthesized NiO NPs [56].</figcaption></figure>
<figure><img src="image_9.png" /><figcaption>**Figure 7:** Mechanisms of plant-mediated metal oxide NP synthesis.</figcaption></figure>

with this method. However, there are limitations to this approach, such as the simple and inexpensive process of skipping purification steps to obtain higher-quality chemicals. The plant extracts are used as renewable and environmentally favorable resources, so they are sustainable [63,64]. Recent advances in bio-inspired materials science have increased interest in studying the interaction between materials science and biological systems. In addition to plants, there are also examples of microbes that synthesize

inorganic compounds; for example, magnetotactic bacteria are useful for synthesizing magnetite NPs [65,66]. However, microbial synthesis was found to be more expensive than synthesis using plant extracts. The screening and cultivation of microorganisms usually take a long time. The mechanism of metal oxide NP synthesis using plant extracts is shown in Figure 7. The various plant extracts used to synthesize the NiO NPs are listed in Table 2.

<table><caption>**Table 2:** Different plant extracts obtained from various plant parts are useful for the synthesis of NiO NPs</caption><thead><tr><td>Plant name</td><td>Precursor</td><td>Size (nm)</td><td>Morphology</td><td>Reference</td></tr></thead><tbody><tr><td>Avicennia Marina leaf extract</td><td>NiCl<sub>2</sub></td><td>30–50</td><td>Flacks</td><td>[67]</td></tr><tr><td>Olive leaves</td><td>Ni(NO<sub>3</sub>)<sub>2</sub></td><td>30–65</td><td>Spherical</td><td>[68]</td></tr><tr><td>Aloe vera</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>—</td><td>—</td><td>[69]</td></tr><tr><td>Lactuca serriola seeds</td><td>NiCl<sub>2</sub>·6H<sub>2</sub>O</td><td>—</td><td>Spherical</td><td>[70]</td></tr><tr><td>Calendula officinalis (leaf)</td><td>NiSO<sub>4</sub>·6H<sub>2</sub>O</td><td>60.39</td><td>Spherical</td><td>[71]</td></tr><tr><td>Abutilon indicum (leaf)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>—</td><td>Cubic</td><td>[72]</td></tr><tr><td>Capparis decidua (leaf)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>—</td><td>Flower</td><td>[73]</td></tr><tr><td>Areca catechu (leaf)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>5–15</td><td>Hexagonal</td><td>[74]</td></tr><tr><td>Nigella sativa (seed)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>10–50</td><td>Spherical</td><td>[75]</td></tr><tr><td>Lantana camara linn (leaf)</td><td>NiCl<sub>2</sub>·6H<sub>2</sub>O</td><td>21</td><td>Hexagonal</td><td>[76]</td></tr><tr><td>Berberis balochistani (stem)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>31.44</td><td>Rhombohedral</td><td>[77]</td></tr><tr><td>Rosemarinus officinalis (leaf)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>8.09</td><td>Quasi-spherical</td><td>[78]</td></tr><tr><td>Opuntia ficus indica (leaf)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>20–35</td><td>Spherical</td><td>[79]</td></tr><tr><td>Limonia acidissima (fruit)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>23</td><td>Spherical</td><td>[80]</td></tr><tr><td>Raphanus sativus (root)</td><td>Ni(CH<sub>3</sub>COOH)<sub>2</sub>·4H<sub>2</sub>O</td><td>34.89</td><td>—</td><td>[81]</td></tr><tr><td>Arabic gum (gum)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>59</td><td>Spherical</td><td>[82]</td></tr><tr><td>Eichhornia crassipes (leaf)</td><td>NiCl<sub>2</sub></td><td>9.1</td><td>Spherical</td><td>[83]</td></tr><tr><td>Limonia acidissima natural fruit juice</td><td>(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>23</td><td>Spherical</td><td>[84]</td></tr><tr><td>Euphorbia heterophylla (L.)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>12–15</td><td>Rhombohedral</td><td>[85]</td></tr><tr><td>Rhamnus triquetra (leaf)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>65</td><td>Spherical</td><td>[86]</td></tr><tr><td>Vernonia amygdalina (leaf)</td><td>NiCl<sub>2</sub>·6H<sub>2</sub>O</td><td>—</td><td>Octahedral</td><td>[87]</td></tr><tr><td>Phoenix dactylifera (Dates)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub></td><td>—</td><td>Rod</td><td>[88]</td></tr><tr><td>Plectranthus amboinicus (leaf)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub></td><td>100</td><td>Spherical</td><td>[89]</td></tr><tr><td>Ananas comosus leaf</td><td>NiCl<sub>2</sub>·6H<sub>2</sub>O</td><td>—</td><td>—</td><td>[90]</td></tr><tr><td>Stevia (leaf)</td><td>Ni(CH<sub>3</sub>COOH)<sub>2</sub>·4H<sub>2</sub>O</td><td>10–40</td><td>Spherical</td><td>[91]</td></tr><tr><td>Solanum trilobatum leaf</td><td>Ni(NO<sub>3</sub>)<sub>2</sub></td><td>25–30</td><td>Cylindrical and rod</td><td>[92]</td></tr><tr><td>Leucas aspera (leaf)</td><td>NiCl<sub>2</sub>·6H<sub>2</sub>O</td><td>—</td><td>Spherical</td><td>[93]</td></tr><tr><td>Allium jesdianum (leaf)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>—</td><td>Spherical</td><td>[94]</td></tr><tr><td>Cydonia oblonga</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>74.5</td><td>—</td><td>[28]</td></tr><tr><td>Zingiber officinale and allium sativum (roots)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub></td><td>&lt;50</td><td>The cubical and more spherical shape</td><td>[95]</td></tr></tbody></table>
<figure><img src="image_10.png" /><figcaption>**Figure 7:** Mechanisms of plant-mediated metal oxide NP synthesis.</figcaption></figure>

with this method. However, there are limitations to this approach, such as the simple and inexpensive process of skipping purification steps to obtain higher-quality chemicals. The plant extracts are used as renewable and environmentally favorable resources, so they are sustainable [63,64]. Recent advances in bio-inspired materials science have increased interest in studying the interaction between materials science and biological systems. In addition to plants, there are also examples of microbes that synthesize

inorganic compounds; for example, magnetotactic bacteria are useful for synthesizing magnetite NPs [65,66]. However, microbial synthesis was found to be more expensive than synthesis using plant extracts. The screening and cultivation of microorganisms usually take a long time. The mechanism of metal oxide NP synthesis using plant extracts is shown in Figure 7. The various plant extracts used to synthesize the NiO NPs are listed in Table 2.

<table><caption>**Table 2:** Different plant extracts obtained from various plant parts are useful for the synthesis of NiO NPs</caption><thead><tr><td>Plant name</td><td>Precursor</td><td>Size (nm)</td><td>Morphology</td><td>Reference</td></tr></thead><tbody><tr><td>Avicennia Marina leaf extract</td><td>NiCl<sub>2</sub></td><td>30–50</td><td>Flacks</td><td>[67]</td></tr><tr><td>Olive leaves</td><td>Ni(NO<sub>3</sub>)<sub>2</sub></td><td>30–65</td><td>Spherical</td><td>[68]</td></tr><tr><td>Aloe vera</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>—</td><td>—</td><td>[69]</td></tr><tr><td>Lactuca serriola seeds</td><td>NiCl<sub>2</sub>·6H<sub>2</sub>O</td><td>—</td><td>Spherical</td><td>[70]</td></tr><tr><td>Calendula officinalis (leaf)</td><td>NiSO<sub>4</sub>·6H<sub>2</sub>O</td><td>60.39</td><td>Spherical</td><td>[71]</td></tr><tr><td>Abutilon indicum (leaf)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>—</td><td>Cubic</td><td>[72]</td></tr><tr><td>Capparis decidua (leaf)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>—</td><td>Flower</td><td>[73]</td></tr><tr><td>Areca catechu (leaf)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>5–15</td><td>Hexagonal</td><td>[74]</td></tr><tr><td>Nigella sativa (seed)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>10–50</td><td>Spherical</td><td>[75]</td></tr><tr><td>Lantana camara linn (leaf)</td><td>NiCl<sub>2</sub>·6H<sub>2</sub>O</td><td>21</td><td>Hexagonal</td><td>[76]</td></tr><tr><td>Berberis balochistani (stem)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>31.44</td><td>Rhombohedral</td><td>[77]</td></tr><tr><td>Rosemarinus officinalis (leaf)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>8.09</td><td>Quasi-spherical</td><td>[78]</td></tr><tr><td>Opuntia ficus indica (leaf)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>20–35</td><td>Spherical</td><td>[79]</td></tr><tr><td>Limonia acidissima (fruit)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>23</td><td>Spherical</td><td>[80]</td></tr><tr><td>Raphanus sativus (root)</td><td>Ni(CH<sub>3</sub>COOH)<sub>2</sub>·4H<sub>2</sub>O</td><td>34.89</td><td>—</td><td>[81]</td></tr><tr><td>Arabic gum (gum)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>59</td><td>Spherical</td><td>[82]</td></tr><tr><td>Eichhornia crassipes (leaf)</td><td>NiCl<sub>2</sub></td><td>9.1</td><td>Spherical</td><td>[83]</td></tr><tr><td>Limonia acidissima natural fruit juice</td><td>(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>23</td><td>Spherical</td><td>[84]</td></tr><tr><td>Euphorbia heterophylla (L.)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>12–15</td><td>Rhombohedral</td><td>[85]</td></tr><tr><td>Rhamnus triquetra (leaf)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>65</td><td>Spherical</td><td>[86]</td></tr><tr><td>Vernonia amygdalina (leaf)</td><td>NiCl<sub>2</sub>·6H<sub>2</sub>O</td><td>—</td><td>Octahedral</td><td>[87]</td></tr><tr><td>Phoenix dactylifera (Dates)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub></td><td>—</td><td>Rod</td><td>[88]</td></tr><tr><td>Plectranthus amboinicus (leaf)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub></td><td>100</td><td>Spherical</td><td>[89]</td></tr><tr><td>Ananas comosus leaf</td><td>NiCl<sub>2</sub>·6H<sub>2</sub>O</td><td>—</td><td>—</td><td>[90]</td></tr><tr><td>Stevia (leaf)</td><td>Ni(CH<sub>3</sub>COOH)<sub>2</sub>·4H<sub>2</sub>O</td><td>10–40</td><td>Spherical</td><td>[91]</td></tr><tr><td>Solanum trilobatum leaf</td><td>Ni(NO<sub>3</sub>)<sub>2</sub></td><td>25–30</td><td>Cylindrical and rod</td><td>[92]</td></tr><tr><td>Leucas aspera (leaf)</td><td>NiCl<sub>2</sub>·6H<sub>2</sub>O</td><td>—</td><td>Spherical</td><td>[93]</td></tr><tr><td>Allium jesdianum (leaf)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>—</td><td>Spherical</td><td>[94]</td></tr><tr><td>Cydonia oblonga</td><td>Ni(NO<sub>3</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td>74.5</td><td>—</td><td>[28]</td></tr><tr><td>Zingiber officinale and allium sativum (roots)</td><td>Ni(NO<sub>3</sub>)<sub>2</sub></td><td>&lt;50</td><td>The cubical and more spherical shape</td><td>[95]</td></tr></tbody></table>
## 2.3 Microbe-mediated synthesis

The essential mechanism for forming NP biogenesis involves the reduction of metal ions by the biomolecules present in living things. This process creates a large number of NPs with well-defined sizes and morphologies that can be isolated from the contaminants. Many researchers applied various techniques for the synthesis of NPs by using bacteria, actinobacteria, viruses, fungi, yeast, and microalgae, as these microorganisms have the innate capability to multiply in various environments [96–102]. Bacteria and microalgae can produce unique nanomaterials such as exopolysaccharides, nanocellulose, and nanowires [103–105]. The production of NPs using microorganisms is far safer than chemical and physical processes [96–102]. Bacteria are preferred over other microorganisms for NP production because they can be cultured in a laboratory setting and their growth rate can be regulated. Microorganisms can adapt to environments with higher metal concentrations and can reduce inorganic elements to NPs via extracellular or intracellular pathways [96]. Microbes take up metal ions from their environment/media and the microorganisms ingest metal ions from the culture media and enzymatically reduce them into their elemental form [106]. During the extracellular synthesis of NPs, the extracellular microbial enzymes, especially the reductase-containing supernatant, are extracted from the microbial culture by centrifugation and allowed to react with the metal ions to synthesize NPs [107–109]. Metal ions are bio-reduced in a cell-free supernatant, resulting in the production of NPs [110]. For microbial

intracellular manufacturing, the cellular mechanism of the microbe is exploited for NP production. Initially, sufficient microbial biomass is obtained by following an appropriate culture protocol [111]. Then, the microbes are supplemented with metal ions and cultured further under optimal conditions for the reduction process, which will be observed by specific chromatic changes. Microbes synthesize NPs as a part of their defense mechanism, as high reactive ion concentrations in their environment are detrimental to their sustainability. To prevent cell death, the microbes use their cellular machinery to convert the reactive ions into a stable form of the respective NPs of reduced ions. Cell damage can occur when the NPs are generated in excessive concentrations. The microbes can tolerate a range of environmental parameters such as ionic strength, pH, temperature, and pressure, but the tolerable range is often limited, and any further change beyond this range due to a longer reaction time can be detrimental to the microbes [42].

# 3 Biological applications

## 3.1 Antibacterial and antifungal activity

The NiO NPs are synthesized with *aloe vera* gel and heated at 300–500°C to study their antibacterial properties, as the free radical nature of NiO NPs can impair microbial cell proliferation [69]. Figure 8(a) shows the zone of inhibition

<figure><img src="image_10.png" /><figcaption>Figure 8: ZOI of NiO NPs against (a) bacterial and (b) fungal strains [69].</figcaption></figure>
## 2.3 Microbe-mediated synthesis

The essential mechanism for forming NP biogenesis involves the reduction of metal ions by the biomolecules present in living things. This process creates a large number of NPs with well-defined sizes and morphologies that can be isolated from the contaminants. Many researchers applied various techniques for the synthesis of NPs by using bacteria, actinobacteria, viruses, fungi, yeast, and microalgae, as these microorganisms have the innate capability to multiply in various environments [96–102]. Bacteria and microalgae can produce unique nanomaterials such as exopolysaccharides, nanocellulose, and nanowires [103–105]. The production of NPs using microorganisms is far safer than chemical and physical processes [96–102]. Bacteria are preferred over other microorganisms for NP production because they can be cultured in a laboratory setting and their growth rate can be regulated. Microorganisms can adapt to environments with higher metal concentrations and can reduce inorganic elements to NPs via extracellular or intracellular pathways [96]. Microbes take up metal ions from their environment/media and the microorganisms ingest metal ions from the culture media and enzymatically reduce them into their elemental form [106]. During the extracellular synthesis of NPs, the extracellular microbial enzymes, especially the reductase-containing supernatant, are extracted from the microbial culture by centrifugation and allowed to react with the metal ions to synthesize NPs [107–109]. Metal ions are bio-reduced in a cell-free supernatant, resulting in the production of NPs [110]. For microbial

intracellular manufacturing, the cellular mechanism of the microbe is exploited for NP production. Initially, sufficient microbial biomass is obtained by following an appropriate culture protocol [111]. Then, the microbes are supplemented with metal ions and cultured further under optimal conditions for the reduction process, which will be observed by specific chromatic changes. Microbes synthesize NPs as a part of their defense mechanism, as high reactive ion concentrations in their environment are detrimental to their sustainability. To prevent cell death, the microbes use their cellular machinery to convert the reactive ions into a stable form of the respective NPs of reduced ions. Cell damage can occur when the NPs are generated in excessive concentrations. The microbes can tolerate a range of environmental parameters such as ionic strength, pH, temperature, and pressure, but the tolerable range is often limited, and any further change beyond this range due to a longer reaction time can be detrimental to the microbes [42].

# 3 Biological applications

## 3.1 Antibacterial and antifungal activity

The NiO NPs are synthesized with *aloe vera* gel and heated at 300–500°C to study their antibacterial properties, as the free radical nature of NiO NPs can impair microbial cell proliferation [69]. Figure 8(a) shows the zone of inhibition

<figure><img src="image_11.png" /><figcaption>**Figure 8:** ZOI of NiO NPs against (a) bacterial and (b) fungal strains [69].</figcaption></figure>
(ZoI) for the antibacterial activity of *Bacillus subtilis*, *Pasteurella multocida*, *Staphylococcus aureus*, and *Escherichia coli*, where the NPs showed significant antibacterial activity against all the tested bacteria. Among all tests, the NiO NPs made from *aloe vera* gel and annealed at 500°C have excellent antibacterial activity. In this, regard the NiO NPs have stronger antibacterial activity toward Gram-negative bacteria than Gram-positive bacteria due to a single layer of peptidoglycan in the Gram-negative bacteria's cell wall, while Gram-positive bacteria have a multi-layered solid peptidoglycan. According to Arokiyaraj et al. [112], the NiO NPs are more effective against Gram-positive bacterial strains. Similarly, the NiO NPs synthesized were tested for antifungal activity against the fungal strains *Aspergillus niger*, *Aspergillus flavus*, and *Penicillium notatum*. The analysis indicated the observation of significant antifungal activity as well. However, this activity is lower than the antibacterial activity due to the increased resistance of fungal strains compared to bacterial strains (Figure 8b).

The particle size of NiO NPs is attributed to its antimicrobial activity, as it improves the NPs' dispersibility and causes cell damage due to the binding of the extracellular $Ni^{2+}$ to the intracellular $Ca^{2+}$ metabolism. The electrostatic interaction between Ni ions and the membrane of a microbial cell is stronger in NPs, resulting in significant activity [113]. The activity is also influenced by the consistency, shape, and size of the NPs [114]. According to a study, NPs change bacteria and fungi's membrane shapes by interacting with them and inhibiting their growth. It disrupts normal mobility during the development of the

plasma membrane, resulting in cell death [115]. Since the prepared NiO NPs have a smaller particle size than micro-sized particles and a high surface area to volume ratio, the NPs react with phosphorus or sulfur in the DNA, stopping protein production and causing cell death [116]. The reactive oxygen species (ROS) structure promotes antimicrobial effects that are part of normal metabolism in living organisms [117]. The onset of ROS destroys cells, which defines the formation of extremely reactive radicals that destroy cell membranes, proteins, the intracellular system, and DNA [118]. The mechanism for the various damages due to the cell lines is shown in Figure 9 [119].

Various mechanisms are proposed for the action mode of MNPs against microbiological organisms, which include (1) cell wall/membrane degradation, (2) MNP-generated oxidative stress, and (3) deterioration/damaging of intracellular proteins due to NP penetration. Because of their nano size, NPs penetrate the intracellular cell matrix, disrupting intracellular absorption and causing cell injury. Electrostatic interactions cause NiO NPs to disrupt cell membranes. Due to electrostatic attraction, the $Ni^{2+}$ ions produced by the NiO NPs interacted with the bacterial cell surfaces of opposite charge and disrupted the cell membrane and its normal physiology and functions. Also, the NPs are so narrow that they can easily pass through the cell wall/membrane and disrupt the cellular components by several routes, which include [120] (1) DNA damage/dysfunction by the interaction of NiO NPs, rendering them unable to perform the regular functions; (2) breaking of hydrogen, oxygen, and phosphate bonds that denature the

<figure><img src="image_11.png" /><figcaption>**Figure 9:** Schematic mechanism of the toxicity effect of NiO NPs against bacteria [119].</figcaption></figure>
(ZoI) for the antibacterial activity of *Bacillus subtilis*, *Pasteurella multocida*, *Staphylococcus aureus*, and *Escherichia coli*, where the NPs showed significant antibacterial activity against all the tested bacteria. Among all tests, the NiO NPs made from *aloe vera* gel and annealed at 500°C have excellent antibacterial activity. In this, regard the NiO NPs have stronger antibacterial activity toward Gram-negative bacteria than Gram-positive bacteria due to a single layer of peptidoglycan in the Gram-negative bacteria's cell wall, while Gram-positive bacteria have a multi-layered solid peptidoglycan. According to Arokiyaraj et al. [112], the NiO NPs are more effective against Gram-positive bacterial strains. Similarly, the NiO NPs synthesized were tested for antifungal activity against the fungal strains *Aspergillus niger*, *Aspergillus flavus*, and *Penicillium notatum*. The analysis indicated the observation of significant antifungal activity as well. However, this activity is lower than the antibacterial activity due to the increased resistance of fungal strains compared to bacterial strains (Figure 8b).

The particle size of NiO NPs is attributed to its antimicrobial activity, as it improves the NPs' dispersibility and causes cell damage due to the binding of the extracellular $Ni^{2+}$ to the intracellular $Ca^{2+}$ metabolism. The electrostatic interaction between Ni ions and the membrane of a microbial cell is stronger in NPs, resulting in significant activity [113]. The activity is also influenced by the consistency, shape, and size of the NPs [114]. According to a study, NPs change bacteria and fungi's membrane shapes by interacting with them and inhibiting their growth. It disrupts normal mobility during the development of the

plasma membrane, resulting in cell death [115]. Since the prepared NiO NPs have a smaller particle size than micro-sized particles and a high surface area to volume ratio, the NPs react with phosphorus or sulfur in the DNA, stopping protein production and causing cell death [116]. The reactive oxygen species (ROS) structure promotes antimicrobial effects that are part of normal metabolism in living organisms [117]. The onset of ROS destroys cells, which defines the formation of extremely reactive radicals that destroy cell membranes, proteins, the intracellular system, and DNA [118]. The mechanism for the various damages due to the cell lines is shown in Figure 9 [119].

Various mechanisms are proposed for the action mode of MNPs against microbiological organisms, which include (1) cell wall/membrane degradation, (2) MNP-generated oxidative stress, and (3) deterioration/damaging of intracellular proteins due to NP penetration. Because of their nano size, NPs penetrate the intracellular cell matrix, disrupting intracellular absorption and causing cell injury. Electrostatic interactions cause NiO NPs to disrupt cell membranes. Due to electrostatic attraction, the $Ni^{2+}$ ions produced by the NiO NPs interacted with the bacterial cell surfaces of opposite charge and disrupted the cell membrane and its normal physiology and functions. Also, the NPs are so narrow that they can easily pass through the cell wall/membrane and disrupt the cellular components by several routes, which include [120] (1) DNA damage/dysfunction by the interaction of NiO NPs, rendering them unable to perform the regular functions; (2) breaking of hydrogen, oxygen, and phosphate bonds that denature the

<figure><img src="image_12.png" /><figcaption>**Figure 9:** Schematic mechanism of the toxicity effect of NiO NPs against bacteria [119].</figcaption></figure>
proteins and associated alteration of protein structure; and
(3) oxidative stress-mediated damage of mitochondria.
Furthermore, these results are consistent with previous
research results that indicate the highly active antibac-
terial activity of NiO NPs against multiple strains of bac-
teria [121–124]. Since NiO NPs have promising bioactivity
in addition to antibacterial activity, they have potential
as medicinal antibacterial agents in the medical sector.
Furthermore, eco-friendly routes for synthetic purposes
must be developed and used to ensure the environmental
safety of green synthetic routes and avoid environmental
pollution. The routes using biological agents are one of the
best solutions to avoid problems associated with conven-
tional synthetic techniques [125,126]. Ali et al. [70] described
the environmentally friendly production of Ni⁰/NiO NPs
using the *Lactuca serriola* seed extract with bactericidal
activity against human pathogenic microorganisms. The sur-
face morphology of the Ni⁰/NiO NPs is shown in Figure 10.
The spherical morphology of the Ni⁰/NiO NPs with a small
agglomeration can be attributed to the induced magnetic
interaction and polymeric adhesion among the NiO/NiO
NPs, as evident from the field emission scanning electron
microscopy (FESEM) images. The antibacterial effect of
MNPs is strongly dependent on size and surface charges
and thus causes changes to the cell membrane and blocks

transport channels. When nano-sized metallic ions reach
the cell, they generate ionization that can disrupt intracel-
lular structures and trigger cell death [127,128]. Multifunc-
tional ROS are formed by the combination of short-lived
oxidants, including superoxide radicals (O²⁻), hydroxyl
radicals (OH⁻), singlet oxygen (O²⁻), and hydrogen peroxide
(H₂O₂) (Figure 11) [129,130]. Due to their extremely high
reactivity, such oxidants produce ROS with the strong
ability to destroy cell membranes, DNA, mRNA, proteins,
ribosomes, and peptidoglycans [131]. In that view, the tra-
ditional disk diffusion method was used to evaluate the
antibacterial activity of Ni⁰/NiO NPs against different cul-
tures of *E. coli*, *S. aureus*, *Staphylococcus epidermidis*,
*Bacillus pumilus*, *B. subtilis*, *Pseudomonas aeruginosa*,
and *Bordetella bronchiseptica* bacteria. From the analysis,
the Ni⁰/NiO NPs at a 20 g/mL concentration showed out-
standing antibacterial efficacy (as compared to the cipro-
floxacin drug) against 7 out of 8 harmful bacteria included
in this study, where a ZoI of 6.05–15.04 mm was observed
[127–130]. Also, the antibacterial activity of Ni⁰/NiO NPs was
investigated against serially diluted bacterial strains with
varying concentrations of Ni⁰/NiO NPs (10 and 20 µg/mL).
The results showed that bacterial growth was significantly
reduced at both concentrations of Ni⁰/NiO NPs, and such an
inhibitory effect on pathogenic bacterial growth by the

<figure><img src="image_12.png" /><figcaption>Figure 10: (a–d) FESEM images of Ni⁰/NiO NPs [70].</figcaption></figure>
proteins and associated alteration of protein structure; and
(3) oxidative stress-mediated damage of mitochondria.
Furthermore, these results are consistent with previous
research results that indicate the highly active antibac-
terial activity of NiO NPs against multiple strains of bac-
teria [121–124]. Since NiO NPs have promising bioactivity
in addition to antibacterial activity, they have potential
as medicinal antibacterial agents in the medical sector.
Furthermore, eco-friendly routes for synthetic purposes
must be developed and used to ensure the environmental
safety of green synthetic routes and avoid environmental
pollution. The routes using biological agents are one of the
best solutions to avoid problems associated with conven-
tional synthetic techniques [125,126]. Ali et al. [70] described
the environmentally friendly production of Ni⁰/NiO NPs
using the *Lactuca serriola* seed extract with bactericidal
activity against human pathogenic microorganisms. The sur-
face morphology of the Ni⁰/NiO NPs is shown in Figure 10.
The spherical morphology of the Ni⁰/NiO NPs with a small
agglomeration can be attributed to the induced magnetic
interaction and polymeric adhesion among the NiO/NiO
NPs, as evident from the field emission scanning electron
microscopy (FESEM) images. The antibacterial effect of
MNPs is strongly dependent on size and surface charges
and thus causes changes to the cell membrane and blocks

transport channels. When nano-sized metallic ions reach
the cell, they generate ionization that can disrupt intracel-
lular structures and trigger cell death [127,128]. Multifunc-
tional ROS are formed by the combination of short-lived
oxidants, including superoxide radicals (O²⁻), hydroxyl
radicals (OH⁻), singlet oxygen (O²⁻), and hydrogen peroxide
(H₂O₂) (Figure 11) [129,130]. Due to their extremely high
reactivity, such oxidants produce ROS with the strong
ability to destroy cell membranes, DNA, mRNA, proteins,
ribosomes, and peptidoglycans [131]. In that view, the tra-
ditional disk diffusion method was used to evaluate the
antibacterial activity of Ni⁰/NiO NPs against different cul-
tures of *E. coli*, *S. aureus*, *Staphylococcus epidermidis*,
*Bacillus pumilus*, *B. subtilis*, *Pseudomonas aeruginosa*,
and *Bordetella bronchiseptica* bacteria. From the analysis,
the Ni⁰/NiO NPs at a 20 g/mL concentration showed out-
standing antibacterial efficacy (as compared to the cipro-
floxacin drug) against 7 out of 8 harmful bacteria included
in this study, where a ZoI of 6.05–15.04 mm was observed
[127–130]. Also, the antibacterial activity of Ni⁰/NiO NPs was
investigated against serially diluted bacterial strains with
varying concentrations of Ni⁰/NiO NPs (10 and 20 µg/mL).
The results showed that bacterial growth was significantly
reduced at both concentrations of Ni⁰/NiO NPs, and such an
inhibitory effect on pathogenic bacterial growth by the

<figure><img src="image_13.png" /><figcaption>Figure 10: (a–d) FESEM images of Ni⁰/NiO NPs [70].</figcaption></figure>
<figure><img src="image_13.png" /><figcaption>**Figure 11:** Different possible mechanisms associated with the antimicrobial activity of Ni⁰/NiO NPs [70].</figcaption></figure>

biologically synthesized Ni⁰/NiO NPs was most likely responsible for the inclusive activity. As a result, Ni⁰/NiO NPs were observed for bacteriostatic activity at low concentrations and bactericidal activity at high concentrations.

Another study used the hot plate combustion method to synthesize NiO NPs, utilizing the *Solanum trilobatum* leaf extract as the fuel and nickel nitrate as the precursor [92]. The high-resolution scanning electron microscopy (HR-SEM) images support the shape of the NiO NPs, as shown in Figure 12. The surface does not have a cylindrical or rod-like form. Some of the elements that influence the morphology attained are the preference of the solvents, capping agents, and experimental parameters such as temperature and time, which affect the reaction mechanism. As a result, the approach used nickel nitrate, and the fuel, an extract of *Solanum trilobatum* leaves, favored the synthesis of NiO NPs with cylindrical and rod-like morphologies. Therefore, it was concluded that the synthesis of NiO NPs with a large surface area and small particle size has made possible by the *Solanum trilobatum* leaf extract, making them suitable for biological applications [92].

Similar to any other cell viability test, the cytotoxicity of NiO NPs prepared using the *Solanum trilobatum* leaf extract was also tested using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay, where the analysis is based on the reduction of the MTT dye to formazan crystals. For example, in a previous study [92], the cell viability of A549 cells was tested using varying concentrations of NiO NPs (up to 1,000 µg/mL), and the results

indicated negligible cell viability losses up to 31.2 µg/mL and a significant reduction above that concentration, meaning that the cell viability is dose-dependent. The fluctuation in percent cell viability in response to NiO NPs at their change of concentrations was observed at change in absorbance which has directly influenced by the number of viable cells [92]. The observed absorbance for the control cells was 0.481 OD (optical dispersion) and 0.083 OD for the cells that reacted with 1,000 µg/mL NiO NPs, indicating that the cells' metabolic activity reduced at the NPs' maximum concentration. Furthermore, to understand the physiological changes occurring to the cells due to NiO NP treatment, morphological studies are performed against the A549 cells at varying concentrations of NiO, as shown in Figure 13(a–d). The regulated cells have a normal, smooth, and uniform morphology, but the cells exposed to NiO NPs have an uneven morphology due to cell division and swelling following death. The extent of cell damage is dose-dependent, and the cell nuclei changed dramatically, indicating that the NiO NPs impact the cell nuclei and their morphology to interrupt regular biochemical functions. The NiO NPs generated ROS and associated oxidative stress, which could decrease the cell's biological activity [132]. For example, following the treatment of A549 cells were observed to have ROS damage. In general, ROS induces DNA damage, a basic site, cell wall damage, oxidized base lesions, breaks single and double strands, and oxidizes proteins and lipids, resulting in the formation of dangerous electrophilic species that alter cellular signal transduction pathways, and lead to cell
<figure><img src="image_14.png" /><figcaption>**Figure 11:** Different possible mechanisms associated with the antimicrobial activity of Ni<sup>0</sup>/NiO NPs [70].</figcaption></figure>

biologically synthesized Ni<sup>0</sup>/NiO NPs was most likely responsible for the inclusive activity. As a result, Ni<sup>0</sup>/NiO NPs were observed for bacteriostatic activity at low concentrations and bactericidal activity at high concentrations.

Another study used the hot plate combustion method to synthesize NiO NPs, utilizing the *Solanum trilobatum* leaf extract as the fuel and nickel nitrate as the precursor [92]. The high-resolution scanning electron microscopy (HR-SEM) images support the shape of the NiO NPs, as shown in Figure 12. The surface does not have a cylindrical or rod-like form. Some of the elements that influence the morphology attained are the preference of the solvents, capping agents, and experimental parameters such as temperature and time, which affect the reaction mechanism. As a result, the approach used nickel nitrate, and the fuel, an extract of *Solanum trilobatum* leaves, favored the synthesis of NiO NPs with cylindrical and rod-like morphologies. Therefore, it was concluded that the synthesis of NiO NPs with a large surface area and small particle size has made possible by the *Solanum trilobatum* leaf extract, making them suitable for biological applications [92].

Similar to any other cell viability test, the cytotoxicity of NiO NPs prepared using the *Solanum trilobatum* leaf extract was also tested using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay, where the analysis is based on the reduction of the MTT dye to formazan crystals. For example, in a previous study [92], the cell viability of A549 cells was tested using varying concentrations of NiO NPs (up to 1,000 µg/mL), and the results

indicated negligible cell viability losses up to 31.2 µg/mL and a significant reduction above that concentration, meaning that the cell viability is dose-dependent. The fluctuation in percent cell viability in response to NiO NPs at their change of concentrations was observed at change in absorbance which has directly influenced by the number of viable cells [92]. The observed absorbance for the control cells was 0.481 OD (optical dispersion) and 0.083 OD for the cells that reacted with 1,000 µg/mL NiO NPs, indicating that the cells' metabolic activity reduced at the NPs' maximum concentration. Furthermore, to understand the physiological changes occurring to the cells due to NiO NP treatment, morphological studies are performed against the A549 cells at varying concentrations of NiO, as shown in Figure 13(a–d). The regulated cells have a normal, smooth, and uniform morphology, but the cells exposed to NiO NPs have an uneven morphology due to cell division and swelling following death. The extent of cell damage is dose-dependent, and the cell nuclei changed dramatically, indicating that the NiO NPs impact the cell nuclei and their morphology to interrupt regular biochemical functions. The NiO NPs generated ROS and associated oxidative stress, which could decrease the cell's biological activity [132]. For example, following the treatment of A549 cells were observed to have ROS damage. In general, ROS induces DNA damage, a basic site, cell wall damage, oxidized base lesions, breaks single and double strands, and oxidizes proteins and lipids, resulting in the formation of dangerous electrophilic species that alter cellular signal transduction pathways, and lead to cell
<figure><img src="image_14.png" /><figcaption>**Figure 12:** (a) HR-SEM image of NiO NPs, (b–d) HR-TEM images of NiO NPs, and (e) SAED pattern of NiO NPs [92].</figcaption></figure>

<figure><img src="image_15.png" /><figcaption>**Figure 13:** (a–d) Morphological changes due to the treatment of varying concentrations of NiO NPs formed using *Solanum trilobatum* leaf extract [92].</figcaption></figure>
<figure><img src="image_15.png" /><figcaption>**Figure 12:** (a) HR-SEM image of NiO NPs, (b–d) HR-TEM images of NiO NPs, and (e) SAED pattern of NiO NPs [92].</figcaption></figure>

<figure><img src="image_16.png" /><figcaption>**Figure 13:** (a–d) Morphological changes due to the treatment of varying concentrations of NiO NPs formed using *Solanum trilobatum* leaf extract [92].</figcaption></figure>
death [133]. In addition, oxidative stress is generated due to electron transfer from ROS such as `OH, H₂O₂, and O₂⁻` [134]. Several studies have also indicated that the metal ions released from the MNPs are a significant component of cytotoxicity [135]. For instance, the Ni²⁺ ions released by the NiO NPs following the treatment of A549 cells were found to induce oxidative stress induction both directly and indirectly, eventually dysfunctioning the mitochondria [136]. Also, the release extent of Ni²⁺ ions is determined by the intrinsic properties of bulk materials, particle size, surface properties, and crystallinity of NiO. Hedberg et al. [137] suggested that the increased metal ion release is associated with ligand-induced metal release processes. They also showed that the Ni²⁺ ions released into the cell culture medium by the NiO particles were absorbed by the A549 cells and further tightly bound to the cell membrane to eventually form stable complexes with various ligands, such as proteins and amino acids. Moreover, the toxicity associated with NiO NPs and the released Ni ions is significantly higher in the nano-sized particles than in the corresponding micro-sized ones [138]. In the nano-sized NiO NPs, considerable cytotoxic effects were observed due to the specific surface area, metal ion-releasing ability, strong physicochemical activities, high crystalline effects, etc. As a result, the NiO nanomaterials thus synthesized by the green synthesis routes serve as promising biomaterials for cytotoxic induction in cancer cell lines (e.g., A549 cells) through oxidative damage by the production of ROS.

## 3.2 Cytotoxicity activity

The NP's research for cancer diagnosis and treatment is increasing nowadays. Sabouri et al. [82] studied the cytotoxic effects of NiO NPs on normal CN cell lines and cancer U87MG cell lines using gum arabic polymer. The analysis results indicated that NiO NPs have contributed to a 50% cancer cell reduction at only 16 µg/mL concentration, thereby confirming this value as the half-maximal inhibitory concentration (IC₅₀). Also, a steep increase in cell viability loss with increased NiO NP concentration was observed, implying that the cytotoxicity is dose-dependent, which can severely impair cancer cell survival. According to the results of this study, the lethal effect of NiO NPs formed by the green synthesis routes is greater in cancer cells than in normal cells, thus supporting the potential role of NiO NPs in cancer treatment. Ghazal et al. [28] used the *Cydonia oblonga* extract to carry out the biosynthesis of NiO NPs in an environmentally friendly and cost-effective manner,

using the same MTT test to understand cell viability and bioavailability [139]. Figure 14 shows FESEM/PSA images of NiO-NPs prepared using an extract of *Cydonia oblonga* at 400°C [28]. According to the SEM results, the sample's morphology, with an average particle size of roughly 74.5 nm, was investigated.

Figure 15 provides the *in vitro* cell viability studies following NiO NP treatment in the concentration range of 0–400 mg/mL, where the results have indicated no significant cytotoxicity up to 400 mg/mL concentration. This suggests that the L929 cells can tolerate the synthesized NPs, thereby indicating their biocompatibility.

Chouke et al. [51] investigated the *in vitro* toxicity of bioinspired NiO NPs on the growth of the B. mori cell line (Bm-17 cells) and the liver cells of *L. rohita* fish, as illustrated in Figure 16. Agar gel electrophoresis was used to assess cell viability, necrotic cell morphology, and DNA damage. NiO NPs promote significant vacuolization in an insect cell line (Bm-17 cells).

## 3.3 Anticancer activity

Kganyago et al. [140] reported the preparation of NiO NPs using the *Monsonia burkeana* plant extract and studied their potential antibacterial activity against numerous bacterial strains and anticancer activity. As shown in Figure 17, the cell viability results analyzed using both MUSE and MTT assays indicated that the treatment of A549 cells with different concentrations of NiO NPs does not affect the viability (>95% of cells are viable) up to a 24 h incubation period. The analysis showed that the plant extract-mediated formation of NiO NPs was ineffective against the lung cancer cells even at high concentrations during the first 24 h period. However, these results contradicted the recent findings and demonstrated that NiO NPs formed with *Moringa olifera* continued to exhibit antiproliferative activity against the HT-29 colon cancer cells. This disparity can be attributed to the changes in phytochemicals in plants such as *Moringa olifera* versus *Monsonia burkeana*, specificity, and incubation time. Also, the kind of cell line matters, as the plant extract used for the formation of NPs has previously been shown to serve as a blood purifier, and it is not surprising that the same plant-derived NPs are effective against bacterial strains. In addition, light microscopy provided morphological analysis of A549 cells, indicating that the plant-derived NiO NPs had no lethal effects on the cells even after 24 h. However, there was a significant effect on the cell growth. Plant-made NiO NPs significantly reduced the development of A549 cells. The
death [133]. In addition, oxidative stress is generated due to electron transfer from ROS such as `OH, H₂O₂, and O₂⁻` [134]. Several studies have also indicated that the metal ions released from the MNPs are a significant component of cytotoxicity [135]. For instance, the Ni²⁺ ions released by the NiO NPs following the treatment of A549 cells were found to induce oxidative stress induction both directly and indirectly, eventually dysfunctioning the mitochondria [136]. Also, the release extent of Ni²⁺ ions is determined by the intrinsic properties of bulk materials, particle size, surface properties, and crystallinity of NiO. Hedberg et al. [137] suggested that the increased metal ion release is associated with ligand-induced metal release processes. They also showed that the Ni²⁺ ions released into the cell culture medium by the NiO particles were absorbed by the A549 cells and further tightly bound to the cell membrane to eventually form stable complexes with various ligands, such as proteins and amino acids. Moreover, the toxicity associated with NiO NPs and the released Ni ions is significantly higher in the nano-sized particles than in the corresponding micro-sized ones [138]. In the nano-sized NiO NPs, considerable cytotoxic effects were observed due to the specific surface area, metal ion-releasing ability, strong physicochemical activities, high crystalline effects, etc. As a result, the NiO nanomaterials thus synthesized by the green synthesis routes serve as promising biomaterials for cytotoxic induction in cancer cell lines (e.g., A549 cells) through oxidative damage by the production of ROS.

## 3.2 Cytotoxicity activity

The NP's research for cancer diagnosis and treatment is increasing nowadays. Sabouri et al. [82] studied the cytotoxic effects of NiO NPs on normal CN cell lines and cancer U87MG cell lines using gum arabic polymer. The analysis results indicated that NiO NPs have contributed to a 50% cancer cell reduction at only 16 µg/mL concentration, thereby confirming this value as the half-maximal inhibitory concentration (IC₅₀). Also, a steep increase in cell viability loss with increased NiO NP concentration was observed, implying that the cytotoxicity is dose-dependent, which can severely impair cancer cell survival. According to the results of this study, the lethal effect of NiO NPs formed by the green synthesis routes is greater in cancer cells than in normal cells, thus supporting the potential role of NiO NPs in cancer treatment. Ghazal et al. [28] used the *Cydonia oblonga* extract to carry out the biosynthesis of NiO NPs in an environmentally friendly and cost-effective manner,

using the same MTT test to understand cell viability and bioavailability [139]. Figure 14 shows FESEM/PSA images of NiO-NPs prepared using an extract of *Cydonia oblonga* at 400°C [28]. According to the SEM results, the sample's morphology, with an average particle size of roughly 74.5 nm, was investigated.

Figure 15 provides the *in vitro* cell viability studies following NiO NP treatment in the concentration range of 0–400 mg/mL, where the results have indicated no significant cytotoxicity up to 400 mg/mL concentration. This suggests that the L929 cells can tolerate the synthesized NPs, thereby indicating their biocompatibility.

Chouke et al. [51] investigated the *in vitro* toxicity of bioinspired NiO NPs on the growth of the B. mori cell line (Bm-17 cells) and the liver cells of *L. rohita* fish, as illustrated in Figure 16. Agar gel electrophoresis was used to assess cell viability, necrotic cell morphology, and DNA damage. NiO NPs promote significant vacuolization in an insect cell line (Bm-17 cells).

## 3.3 Anticancer activity

Kganyago et al. [140] reported the preparation of NiO NPs using the *Monsonia burkeana* plant extract and studied their potential antibacterial activity against numerous bacterial strains and anticancer activity. As shown in Figure 17, the cell viability results analyzed using both MUSE and MTT assays indicated that the treatment of A549 cells with different concentrations of NiO NPs does not affect the viability (>95% of cells are viable) up to a 24 h incubation period. The analysis showed that the plant extract-mediated formation of NiO NPs was ineffective against the lung cancer cells even at high concentrations during the first 24 h period. However, these results contradicted the recent findings and demonstrated that NiO NPs formed with *Moringa olifera* continued to exhibit antiproliferative activity against the HT-29 colon cancer cells. This disparity can be attributed to the changes in phytochemicals in plants such as *Moringa olifera* versus *Monsonia burkeana*, specificity, and incubation time. Also, the kind of cell line matters, as the plant extract used for the formation of NPs has previously been shown to serve as a blood purifier, and it is not surprising that the same plant-derived NPs are effective against bacterial strains. In addition, light microscopy provided morphological analysis of A549 cells, indicating that the plant-derived NiO NPs had no lethal effects on the cells even after 24 h. However, there was a significant effect on the cell growth. Plant-made NiO NPs significantly reduced the development of A549 cells. The
<figure><img src="image_16.png" /><figcaption>**Figure 14:** (a–c) FESEM images and (d) PSA of NiO-NPs [28].</figcaption></figure>

morphological form of untreated and treated A549 cells is shown in Figure 18(a–d). The green circles indicate that both groups retained the usual epithelial cell shape. The NiO NPs do not affect the morphology of A549 cells and show no

cytotoxicity toward A549 in both treatments, as confirmed by the viability profile data. However, treated cells have more space than the corresponding cells without any treatment. Observing some cells with classic apoptotic features (e.g., red circles) can be linked to the natural cell death associated with cell cycles. NiO NPs produced from *Monsonia burkeana* do not affect the viability of non-cancerous HEK 293 cells of the embryonic kidney, thereby supporting the fact that the particles have the potential for the sustainable treatment of cancer and are non-harmful even if consumed.

<figure><img src="image_17.png" /><figcaption>**Figure 15:** Cytotoxicity studies of varying concentrations of NiO NPs (up to 400 µg/mL) by MTT assay [28].</figcaption></figure>

## 3.4 Antioxidant properties of NiO NPs against DPPH

Zhang et al. [71] effectively prepared NiO NPs in an aqueous medium using the *Calendula officinalis* leaf extract. They also tested the DPPH radical scavenging potentials of particles coated with the leaf extract by comparing them with BHT as a typical antioxidant. In general, free radicals are species that do not have a complete electron shell and
<figure><img src="image_17.png" /><figcaption>**Figure 14:** (a–c) FESEM images and (d) PSA of NiO-NPs [28].</figcaption></figure>

morphological form of untreated and treated A549 cells is shown in Figure 18(a–d). The green circles indicate that both groups retained the usual epithelial cell shape. The NiO NPs do not affect the morphology of A549 cells and show no

cytotoxicity toward A549 in both treatments, as confirmed by the viability profile data. However, treated cells have more space than the corresponding cells without any treatment. Observing some cells with classic apoptotic features (e.g., red circles) can be linked to the natural cell death associated with cell cycles. NiO NPs produced from *Monsonia burkeana* do not affect the viability of non-cancerous HEK 293 cells of the embryonic kidney, thereby supporting the fact that the particles have the potential for the sustainable treatment of cancer and are non-harmful even if consumed.

<figure><img src="image_18.png" /><figcaption>**Figure 15:** Cytotoxicity studies of varying concentrations of NiO NPs (up to 400 µg/mL) by MTT assay [28].</figcaption></figure>

## 3.4 Antioxidant properties of NiO NPs against DPPH

Zhang et al. [71] effectively prepared NiO NPs in an aqueous medium using the *Calendula officinalis* leaf extract. They also tested the DPPH radical scavenging potentials of particles coated with the leaf extract by comparing them with BHT as a typical antioxidant. In general, free radicals are species that do not have a complete electron shell and
<figure><img src="image_18.png" /><figcaption>**Figure 16:** Schematic representation of *in vitro* toxicity of bioinspired NiO NPs [51].</figcaption></figure>

<figure><img src="image_19.png" /><figcaption>**Figure 17:** Flow cytometry studies of A549 cells following the treatment of NiO NPs at different profiles of (a) untreated, (b) 125 µg/mL, (c) 250 µg/mL, and (d) 500 µg/mL [140].</figcaption></figure>
<figure><img src="image_19.png" /><figcaption>**Figure 16:** Schematic representation of *in vitro* toxicity of bioinspired NiO NPs [51].</figcaption></figure>

<figure><img src="image_20.png" /><figcaption>**Figure 17:** Flow cytometry studies of A549 cells following the treatment of NiO NPs at different profiles of (a) untreated, (b) 125 µg/mL, (c) 250 µg/mL, and (d) 500 µg/mL [140].</figcaption></figure>
<figure><img src="image_20.png" /><figcaption>**Figure 18:** Morphological observation of A549 cells: (a) untreated, (b) 125 µg/mL, (c) 250 µg/mL, and (d) 500 µg/mL NiO NP treatment [140].</figcaption></figure>

can speed up chemical reactions more than others. They develop when the human body is exposed to cigarette smoke and radiation. The main human free radical is oxygen. When an oxygen (O₂) molecule is exposed to radiation, it steals an electron from other molecules, destroying DNA and other molecules. These changes can lead to chronic diseases such as heart disease, muscle failure, diabetes, and cancer [141]. Antioxidants, which act like a broom against free radicals, are recognized as effective treatments for destroying free radicals and regenerating damaged cells. More importantly, laboratory evidence suggests that antioxidants can significantly reduce cancer risk [57,142–144]. Aqueous leaf extracts of C. officinalis, BHT, and NiO NPs have IC₅₀ of 328, 204, and 192 mg/mL, respectively (Figure 19). The MNPs have high potential for DPPH inhibition. The results of our investigation are consistent with many other studies examining the mutual effects of herbs and metal salts on anti-oxidant capacity against DPPH [57,142–144]. In general, MNPs have outstanding antioxidant properties, with the antioxidant properties of NiO NPs being well documented. When NiO NPs are made from medicinal plants, the Ni element forms a powerful compound with phenolic and flavonoid chemicals, resulting in unique antioxidant properties.

### 3.4.1 DPPH radical scavenging assay

Kumar et al. [84] demonstrated a facile green synthesis of NiO NPs using the natural *Limonia acidissima* fruit juice via a solution combustion technique. Antioxidants are characterized by their ability to scavenge free radicals. Another important characteristic of antioxidants is their ability to donate hydrogen or electrons to oxidizing agents. DPPH is a stable free radical with an unpaired electron on the nitrogen atom and an absorbance of 517 nm (a deep violet color). The color changed to yellow when the odd electron was connected to the DPPH [145]. The ability of antioxidant molecules to donate hydrogen is required for scavenging free radicals [146]. The radical scavenging activity of NiO NPs against DPPH is significant (Figure 20a). In addition, as NiO NPs were prepared by combustion using the *Limonia acidissima* fruit juice, with a possibility of phytochemical adsorption on their surface. Compared to the reference substance, BHT, NiO NPs proved to be more effective. The antioxidant activity of NiO NPs is comparable (2.73 µg/mL) to that of the reference chemical BHT (2.21 µg/mL). NiO NPs have significant hydroxyl radical scavenging activity (Figure 20b).
<figure><img src="image_21.png" /><figcaption>**Figure 18:** Morphological observation of A549 cells: (a) untreated, (b) 125 µg/mL, (c) 250 µg/mL, and (d) 500 µg/mL NiO NP treatment [140].</figcaption></figure>

can speed up chemical reactions more than others. They develop when the human body is exposed to cigarette smoke and radiation. The main human free radical is oxygen. When an oxygen (O₂) molecule is exposed to radiation, it steals an electron from other molecules, destroying DNA and other molecules. These changes can lead to chronic diseases such as heart disease, muscle failure, diabetes, and cancer [141]. Antioxidants, which act like a broom against free radicals, are recognized as effective treatments for destroying free radicals and regenerating damaged cells. More importantly, laboratory evidence suggests that antioxidants can significantly reduce cancer risk [57,142–144]. Aqueous leaf extracts of C. officinalis, BHT, and NiO NPs have IC₅₀ of 328, 204, and 192 mg/mL, respectively (Figure 19). The MNPs have high potential for DPPH inhibition. The results of our investigation are consistent with many other studies examining the mutual effects of herbs and metal salts on anti-oxidant capacity against DPPH [57,142–144]. In general, MNPs have outstanding antioxidant properties, with the antioxidant properties of NiO NPs being well documented. When NiO NPs are made from medicinal plants, the Ni element forms a powerful compound with phenolic and flavonoid chemicals, resulting in unique antioxidant properties.

### 3.4.1 DPPH radical scavenging assay

Kumar et al. [84] demonstrated a facile green synthesis of NiO NPs using the natural *Limonia acidissima* fruit juice via a solution combustion technique. Antioxidants are characterized by their ability to scavenge free radicals. Another important characteristic of antioxidants is their ability to donate hydrogen or electrons to oxidizing agents. DPPH is a stable free radical with an unpaired electron on the nitrogen atom and an absorbance of 517 nm (a deep violet color). The color changed to yellow when the odd electron was connected to the DPPH [145]. The ability of antioxidant molecules to donate hydrogen is required for scavenging free radicals [146]. The radical scavenging activity of NiO NPs against DPPH is significant (Figure 20a). In addition, as NiO NPs were prepared by combustion using the *Limonia acidissima* fruit juice, with a possibility of phytochemical adsorption on their surface. Compared to the reference substance, BHT, NiO NPs proved to be more effective. The antioxidant activity of NiO NPs is comparable (2.73 µg/mL) to that of the reference chemical BHT (2.21 µg/mL). NiO NPs have significant hydroxyl radical scavenging activity (Figure 20b).
<figure><img src="image_21.png" /><figcaption>**Figure 19:** (a) Comparison of the antioxidant nature of NiSO₄, (b) aqueous extract of C. officinalis, (c) NiO NPs, and (d) BHT against DPPH [71].</figcaption></figure>

<figure><img src="image_22.png" /><figcaption>**Figure 20:** Comparison of antioxidation effects of NiO NPs by (a) DPPH radicals and (b) hydroxyl radicals [84].</figcaption></figure>
<figure><img src="image_22.png" /><figcaption>**Figure 19:** (a) Comparison of the antioxidant nature of NiSO₄, (b) aqueous extract of C. officinalis, (c) NiO NPs, and (d) BHT against DPPH [71].</figcaption></figure>

<figure><img src="image_23.png" /><figcaption>**Figure 20:** Comparison of antioxidation effects of NiO NPs by (a) DPPH radicals and (b) hydroxyl radicals [84].</figcaption></figure>
<figure><img src="image_23.png" /><figcaption>**Figure 21:** (a and b) CAM model assay provided suppression of *in vivo* angiogenesis by NiO NPs [84].</figcaption></figure>

<figure><img src="image_24.png" /><figcaption>**Figure 22:** (a and b) Comparison of antimicrobial potentials of various NiO NP-based composites [77].</figcaption></figure>
<figure><img src="image_24.png" /><figcaption>**Figure 21:** (a and b) CAM model assay provided suppression of *in vivo* angiogenesis by NiO NPs [84].</figcaption></figure>

<figure><img src="image_25.png" /><figcaption>**Figure 22:** (a and b) Comparison of antimicrobial potentials of various NiO NP-based composites [77].</figcaption></figure>
### 3.4.2 Angioinhibitory effect by NiO NPs

Figure 21 shows the autoinhibitory effect of NiO NPs, where the analysis showed a significantly progressive result in the chorioallantoic membrane (CAM) test model of growing embryos. The data show the results of six eggs in one batch. The anti-angiogenic effect of NiO NPs was examined and shown to have excellently slowed the proliferation of capillaries near the area of disks containing NiO NPs compared to controls (Figure 21).

### 3.5 Antifungal activity of phytofabricated NiO NPs

Uddin et al. [77] developed a green biogenic approach for the green production of NiO NPs using the phytochemical-rich strain extract of *Berberis balochistanica* (BBS). The anti-bacterial activity of phytofabricated BBS-NiO NPs (100, 500, and 1,000 g/mL) against the bacterial strains *Proteus vulgaris* and *Staphylococcus aureus* is shown in Figure 22a. BBS-NiO NPs showed a dose-dependent response to both bacterial strains tested. In addition, for antibacterial activities, it was found that 10 g of ciprofloxacin (a positive control) was more reactive than any BBS-NiO NPs used. BBS-NiO NPs were tested for antifungal activity against *Fusarium oxysporum*, *Aspergillus niger*, and *Alternaria alternata* at different doses (50, 100, 500, and 1,000 µg/mL). There were dose-dependent responses against all three fungal strains studied (Figure 22b). *F. oxysporum* showed less susceptibility at high concentrations (1,000 µg/mL), while *A. alternata* showed the highest level of susceptibility (71.25% inhibition), followed by *A. niger* (39.51% inhibition).

## 4 Conclusions and future perspectives

Green synthesis is by far the most environmentally friendly method for producing NPs, using plant sources and microbes as redox mediators to convert metal cations into metal/metal oxide NPs. Plant and microbial extracts contain a variety of phytochemicals and metabolites that act as stabilizers for biosynthesized NPs by acting as capping agents. The advantages of green synthesis over standard synthetic methods include low cost, safety, and environmental friendliness, justifying the growing interest in green synthesis over the past few decades. Many recent investigations on the preparation of NiO NPs by plant-mediated green synthesis are discussed

and covered in this review. Many of these are medicinal plants with established therapeutic uses. Synthetic techniques using plant and microbial extracts and the characterization and performance of the bio-synthesized NiO NPs are briefly described, highlighting their promise in photocatalysis and biomedical applications. The main advantages of more environmentally friendly approaches are low cost and the use of antimicrobial NP combinations, allowing natural plant extracts where the synthesis approach does not require toxic chemicals as reducing agents, as well as new uses such as antibacterial bandages. A thorough understanding of the wide range of microbial/biochemical constituents is required, as well as the various routes of laboratory synthesis, including the isolation and tracing of components used in the precise reduction of multiple metal salts to the required materials. Future challenges and achievements related to green prospects for manufacturing nanomaterials need to be addressed by expanding laboratory-based compliance to a feasible industrial level by considering current and past health and environmental impacts. On the other hand, a more environmentally friendly approach based on bio-derived materials or nanomaterials is needed and will be widely used in the field of environmental remediation as well as in other broad fields such as the food, cosmetics, and pharmaceutical industries. In addition, biomaterials from marine plants and algae isolated from specific regions have yet to be discovered. As a result, there are several potential avenues for developing novel green techniques based on biogenic synthesis. A significant amount of scientific research is required to enable the industrial production of green nanomaterials. The eventual release of such nanomaterials into the environment could result in unusual behavior, which is a concern that requires further research.

**Funding information:** Authors state no funding involved.

**Author contributions:** S.S. – conceptualization; S.S., I.F., A.L.J., Z.R.M., E.L. and W.C.O. – data curation; S.S., I.F., A.L.J. and Z.R.M – formal analysis; I.F., A.L.J., Z.R.M., E.L. and W.C.O – validation; I.F. and E.L. – visualization; Z.R.M – investigation; W.C.O – funding acquisition.

**Conflict of interest:** The authors declare no conflict of interest.

**Ethical approval:** The conducted research is not related to either human or animals use.

**Data availability statement:** The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
### 3.4.2 Angioinhibitory effect by NiO NPs

Figure 21 shows the autoinhibitory effect of NiO NPs, where the analysis showed a significantly progressive result in the chorioallantoic membrane (CAM) test model of growing embryos. The data show the results of six eggs in one batch. The anti-angiogenic effect of NiO NPs was examined and shown to have excellently slowed the proliferation of capillaries near the area of disks containing NiO NPs compared to controls (Figure 21).

### 3.5 Antifungal activity of phytofabricated NiO NPs

Uddin et al. [77] developed a green biogenic approach for the green production of NiO NPs using the phytochemical-rich strain extract of *Berberis balochistanica* (BBS). The anti-bacterial activity of phytofabricated BBS-NiO NPs (100, 500, and 1,000 g/mL) against the bacterial strains *Proteus vulgaris* and *Staphylococcus aureus* is shown in Figure 22a. BBS-NiO NPs showed a dose-dependent response to both bacterial strains tested. In addition, for antibacterial activities, it was found that 10 g of ciprofloxacin (a positive control) was more reactive than any BBS-NiO NPs used. BBS-NiO NPs were tested for antifungal activity against *Fusarium oxysporum*, *Aspergillus niger*, and *Alternaria alternata* at different doses (50, 100, 500, and 1,000 µg/mL). There were dose-dependent responses against all three fungal strains studied (Figure 22b). *F. oxysporum* showed less susceptibility at high concentrations (1,000 µg/mL), while *A. alternata* showed the highest level of susceptibility (71.25% inhibition), followed by *A. niger* (39.51% inhibition).

## 4 Conclusions and future perspectives

Green synthesis is by far the most environmentally friendly method for producing NPs, using plant sources and microbes as redox mediators to convert metal cations into metal/metal oxide NPs. Plant and microbial extracts contain a variety of phytochemicals and metabolites that act as stabilizers for biosynthesized NPs by acting as capping agents. The advantages of green synthesis over standard synthetic methods include low cost, safety, and environmental friendliness, justifying the growing interest in green synthesis over the past few decades. Many recent investigations on the preparation of NiO NPs by plant-mediated green synthesis are discussed

and covered in this review. Many of these are medicinal plants with established therapeutic uses. Synthetic techniques using plant and microbial extracts and the characterization and performance of the bio-synthesized NiO NPs are briefly described, highlighting their promise in photocatalysis and biomedical applications. The main advantages of more environmentally friendly approaches are low cost and the use of antimicrobial NP combinations, allowing natural plant extracts where the synthesis approach does not require toxic chemicals as reducing agents, as well as new uses such as antibacterial bandages. A thorough understanding of the wide range of microbial/biochemical constituents is required, as well as the various routes of laboratory synthesis, including the isolation and tracing of components used in the precise reduction of multiple metal salts to the required materials. Future challenges and achievements related to green prospects for manufacturing nanomaterials need to be addressed by expanding laboratory-based compliance to a feasible industrial level by considering current and past health and environmental impacts. On the other hand, a more environmentally friendly approach based on bio-derived materials or nanomaterials is needed and will be widely used in the field of environmental remediation as well as in other broad fields such as the food, cosmetics, and pharmaceutical industries. In addition, biomaterials from marine plants and algae isolated from specific regions have yet to be discovered. As a result, there are several potential avenues for developing novel green techniques based on biogenic synthesis. A significant amount of scientific research is required to enable the industrial production of green nanomaterials. The eventual release of such nanomaterials into the environment could result in unusual behavior, which is a concern that requires further research.

**Funding information:** Authors state no funding involved.

**Author contributions:** S.S. – conceptualization; S.S., I.F., A.L.J., Z.R.M., E.L. and W.C.O. – data curation; S.S., I.F., A.L.J. and Z.R.M – formal analysis; I.F., A.L.J., Z.R.M., E.L. and W.C.O – validation; I.F. and E.L. – visualization; Z.R.M – investigation; W.C.O – funding acquisition.

**Conflict of interest:** The authors declare no conflict of interest.

**Ethical approval:** The conducted research is not related to either human or animals use.

**Data availability statement:** The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
References

[1] Garibo D, Borbón-Nuñez HA, de León JN, García Mendoza E, Estrada I, Toledano-Magaña Y, et al. Green Synthesis of Silver Nanoparticles using Lysiloma acapulcensis Exhibit High-antimicrobial Activity. Sci Rep. 2020;10:1–11.

[2] Muthukumaran M, Dhinagaran G, Venkatachalam K, Sagadevan S, Gunasekaran S, Podder J, et al. Green synthesis of cuprous oxide nanoparticles for environmental remediation and enhanced visible-light photocatalytic activity. Optik. 2020;214:164849.

[3] Rathinabala R, Thamizselvi R, Padmanabhan D, Alshahateet SF, Fatimah I, Sibhatu AK, et al. Sun light-assisted enhanced photocatalytic activity and cytotoxicity of green synthesized SnO₂ nanoparticles. Inorg Chem Commun. 2022;143:109783.

[4] Hariharan D, Thangamuniyandi P, Christy AJ, Vasantharaja R, Selvakumar P, Sagadevan S, et al. Enhanced photocatalysis and anticancer activity of green hydrothermal synthesized Ag@TiO₂ nanoparticles. J Photochem Photobiol B: Biol. 2020;202:111636.

[5] Koteeswari P, Sagadevan S, Fatimah I, Sibhatu AK, Abd Razak SI, Leonard E, et al. Green synthesis and characterization of copper oxide nanoparticles and their photocatalytic activity. Inorg Chem Commun. 2022;144:109851.

[6] Sudhasree S, Shakila Banu A, Brindha P, Kurian GA. Synthesis of nickel nanoparticles by chemical and green route and their comparison in respect to biological effect and toxicity. Toxicol Environ Chem. 2014;96:743–54.

[7] Wang H, Gong Q, Huang H, Gao T, Yuan Z, Zhou G. Pn hetero-structured TiO₂/NiO double-shelled hollow spheres for the photocatalytic degradation of papermaking wastewater. Mater Res Bull. 2018;107:397–406.

[8] Sagadevan S, Vennila S, Muthukrishnan L, Gurunathan K, Oh WC, Paiman S, et al. Exploring the therapeutic potentials of phyto-mediated silver nanoparticles formed via Calotropis procera (Ait.) R. Br. root extract. J Exp Nanosci. 2020;15(1):217–31.

[9] Han K, Huang H, Gong Q, Si T, Zhang Z, Zhou G. Temperature-induced hierarchical Tremella-like and Pinecone-like NiO microspheres for high-performance supercapacitor electrode materials. J Mater Sci. 2018;53:12477–91.

[10] Sagadevan S, Imteyaz S, Murugan B, Anita Lett J, Sridewi N, Weldegebriele GK, et al. Oh, A comprehensive review on green synthesis of titanium dioxide nanoparticles and their diverse biomedical applications. Green Process Synth. 2022;11(1):44–63.

[11] Sun B, Zhang Y, Zhang R, Yu H, Zhou G, Zhang H, et al. High-Order Nonlinear Optical Properties Generated by Different Electron Transition Processes of NiO Nanosheets and Applications to Ultrafast Lasers. Adv Optical Mater. 2017;5:1600937–9218.

[12] Suresh S, Vennila S, Anita Lett J, Fatimah I, Mohammad F, Al-Lohedan HA, et al. Star fruit extract-mediated green synthesis of metal oxide nanoparticles. Inorg Nano-Metal Chem. 2022;52(2):173–80.

[13] Fatimah I, Purwiandono G, Jauhari MH, Maharani AA, Sagadevan S, Oh WC, et al. Synthesis and control of the morphology of SnO₂ nanoparticles via various concentrations of Tinospora cordifolia stem extract and reduction methods. Arab J Chem. 2022;15(4):103738.

[14] Muthukrishnan L, Chellappa M, Nanda A, Thukkaram S, Selvaraj G, Muthiah B, et al. Bio-fabrication of pigment-capped silver nanoparticles encountering antibiotic-resistant strains and

their cytotoxic effect towards human epidermoid larynx carcinoma (HEp-2) cells. RSC Adv. 2019;9(28):15874–86.

[15] Sagadevan S, Vennila S, Singh P, Lett JA, Johan MR, Marlinda AR, et al. Facile synthesis of silver nanoparticles using Averrhoa bilimbi L and Plum extracts and investigation on the synergistic bioactivity using in vitro models. Green Process Synth. 2019;8(1):873–84.

[16] Ibrahim HMM. Green synthesis and characterization of silver nanoparticles using banana peel extract and their antimicrobial activity against representative microorganisms. J Radiat Res Appl Sci. 2015;8:265–75.

[17] Sun B, Zhou G, Gao T, Zhang H, Yu H. NiO nanosheet/TiO₂ nanorod-constructed p–n heterostructures for improved photocatalytic activity. Appl Surf Sci. 2016;364:322–31.

[18] Akhtar MS, Panwar J, Yun YS. Biogenic synthesis of metallic nanoparticles by plant extracts, ACS Sustain. Chem Eng. 2013;1:591–602.

[19] Soumya V, Indira YM, Venkatesh P, Hariprasath K. A novelmethod of extraction of bamboo seed oil (Bambusa bambos Druce) and its promising effect on metabolic symptoms of experimentally induced polycystic ovarian disease. Indian J Pharm. 2014;48:162–7.

[20] Elango G, Kumaran SM, Kumar SS, Muthuraja S, Roopan SM. Green synthesis of SnO₂ nanoparticles and its photocatalytic activity of phenolsulfonphthalein dye. Spectrochim Acta A. 2015;145:176–80.

[21] Iravani S. Green synthesis of metal nanoparticles using plants. Green Chem. 2011;13:2638–50.

[22] Patete JM, Peng X, Koenigsmann C, Xu Y, Karnb B, Wong SS. Viable methodologies for the synthesis of high-quality nanostructures. Green Chem. 2011;13:482–519.

[23] Susan A, Mansor BA, Farideh N, Rosfarizan M. Green biosynthesis and characterization of zinc oxide nanoparticles using brown marine macroalga Sargassum muticum aqueous extract. Mater Lett. 2014;116:275–7.

[24] Kouvaris P, Andreas D, Vassilis Z, Dimitrios P, Sofia AT, Michailidis N. Green synthesis and characterization of silver nanoparticles produced using Arbutus unedo leaf extract. Mater Lett. 2012;76:18–20.

[25] Manukyan KV, Avetisyan AG, Shuck CE, Chatilyan HA, Rouvimov S, Kharatyan SL, et al. Nickel oxide reduction by hydrogen: kinetics and structural transformations. J Phys Chem C. 2015;119(28):16131–8.

[26] Bonomo M. Synthesis and characterization of NiO nanostructures: a review. J Nanopart Res. 2018;20:222.

[27] Tientong J, Garcia S, Thurber CR, Golden TD. Synthesis of nickel and nickel hydroxide nanopowder by simplified chemical reduction. J Nanotechnol. 2014;2014:1–6.

[28] Ghazal S, Akbari A, Hosseini HA, Sabouri Z, Forouzanfar F, Khatami M, et al. Sol-gel biosynthesis of nickel oxide nanoparticles using Cydonia oblonga extract and evaluation of their cytotoxicity and photocatalytic activities. J Mol Struct. 2020;1217:128378.

[29] Vardhan KH, Kumar PS, Panda RC. A review on heavy metal pollution, toxicity and remedial measures: Current trends and future perspectives. J Mol Liq. 2019;290:111197.

[30] Genchi G, Carocci A, Lauria G, Sinicropi MS, Catalano A. Nickel: Human Health and Environmental Toxicology. Int J Environ Res Public Health. 2020 Jan 21;17(3):679. doi: 10.3390/ijerph17030679.

[31] Venkitanarayanan K, Thakur S, Ricke SC, editors. Food safety in poultry meat production. Cham, Switzerland: Springer International Publishing; 2019.
References

[1] Garibo D, Borbón-Nuñez HA, de León JN, García Mendoza E, Estrada I, Toledano-Magaña Y, et al. Green Synthesis of Silver Nanoparticles using Lysiloma acapulcensis Exhibit High-antimicrobial Activity. Sci Rep. 2020;10:1–11.

[2] Muthukumaran M, Dhinagaran G, Venkatachalam K, Sagadevan S, Gunasekaran S, Podder J, et al. Green synthesis of cuprous oxide nanoparticles for environmental remediation and enhanced visible-light photocatalytic activity. Optik. 2020;214:164849.

[3] Rathinabala R, Thamizselvi R, Padmanabhan D, Alshahateet SF, Fatimah I, Sibhatu AK, et al. Sun light-assisted enhanced photocatalytic activity and cytotoxicity of green synthesized SnO₂ nanoparticles. Inorg Chem Commun. 2022;143:109783.

[4] Hariharan D, Thangamuniyandi P, Christy AJ, Vasantharaja R, Selvakumar P, Sagadevan S, et al. Enhanced photocatalysis and anticancer activity of green hydrothermal synthesized Ag@TiO₂ nanoparticles. J Photochem Photobiol B: Biol. 2020;202:111636.

[5] Koteeswari P, Sagadevan S, Fatimah I, Sibhatu AK, Abd Razak SI, Leonard E, et al. Green synthesis and characterization of copper oxide nanoparticles and their photocatalytic activity. Inorg Chem Commun. 2022;144:109851.

[6] Sudhasree S, Shakila Banu A, Brindha P, Kurian GA. Synthesis of nickel nanoparticles by chemical and green route and their comparison in respect to biological effect and toxicity. Toxicol Environ Chem. 2014;96:743–54.

[7] Wang H, Gong Q, Huang H, Gao T, Yuan Z, Zhou G. Pn hetero-structured TiO₂/NiO double-shelled hollow spheres for the photocatalytic degradation of papermaking wastewater. Mater Res Bull. 2018;107:397–406.

[8] Sagadevan S, Vennila S, Muthukrishnan L, Gurunathan K, Oh WC, Paiman S, et al. Exploring the therapeutic potentials of phyto-mediated silver nanoparticles formed via Calotropis procera (Ait.) R. Br. root extract. J Exp Nanosci. 2020;15(1):217–31.

[9] Han K, Huang H, Gong Q, Si T, Zhang Z, Zhou G. Temperature-induced hierarchical Tremella-like and Pinecone-like NiO microspheres for high-performance supercapacitor electrode materials. J Mater Sci. 2018;53:12477–91.

[10] Sagadevan S, Imteyaz S, Murugan B, Anita Lett J, Sridewi N, Weldegebriele GK, et al. Oh, A comprehensive review on green synthesis of titanium dioxide nanoparticles and their diverse biomedical applications. Green Process Synth. 2022;11(1):44–63.

[11] Sun B, Zhang Y, Zhang R, Yu H, Zhou G, Zhang H, et al. High-Order Nonlinear Optical Properties Generated by Different Electron Transition Processes of NiO Nanosheets and Applications to Ultrafast Lasers. Adv Optical Mater. 2017;5:1600937–9218.

[12] Suresh S, Vennila S, Anita Lett J, Fatimah I, Mohammad F, Al-Lohedan HA, et al. Star fruit extract-mediated green synthesis of metal oxide nanoparticles. Inorg Nano-Metal Chem. 2022;52(2):173–80.

[13] Fatimah I, Purwiandono G, Jauhari MH, Maharani AA, Sagadevan S, Oh WC, et al. Synthesis and control of the morphology of SnO₂ nanoparticles via various concentrations of Tinospora cordifolia stem extract and reduction methods. Arab J Chem. 2022;15(4):103738.

[14] Muthukrishnan L, Chellappa M, Nanda A, Thukkaram S, Selvaraj G, Muthiah B, et al. Bio-fabrication of pigment-capped silver nanoparticles encountering antibiotic-resistant strains and

their cytotoxic effect towards human epidermoid larynx carcinoma (HEp-2) cells. RSC Adv. 2019;9(28):15874–86.

[15] Sagadevan S, Vennila S, Singh P, Lett JA, Johan MR, Marlinda AR, et al. Facile synthesis of silver nanoparticles using Averrhoa bilimbi L and Plum extracts and investigation on the synergistic bioactivity using in vitro models. Green Process Synth. 2019;8(1):873–84.

[16] Ibrahim HMM. Green synthesis and characterization of silver nanoparticles using banana peel extract and their antimicrobial activity against representative microorganisms. J Radiat Res Appl Sci. 2015;8:265–75.

[17] Sun B, Zhou G, Gao T, Zhang H, Yu H. NiO nanosheet/TiO₂ nanorod-constructed p–n heterostructures for improved photocatalytic activity. Appl Surf Sci. 2016;364:322–31.

[18] Akhtar MS, Panwar J, Yun YS. Biogenic synthesis of metallic nanoparticles by plant extracts, ACS Sustain. Chem Eng. 2013;1:591–602.

[19] Soumya V, Indira YM, Venkatesh P, Hariprasath K. A novelmethod of extraction of bamboo seed oil (Bambusa bambos Druce) and its promising effect on metabolic symptoms of experimentally induced polycystic ovarian disease. Indian J Pharm. 2014;48:162–7.

[20] Elango G, Kumaran SM, Kumar SS, Muthuraja S, Rooper SM. Green synthesis of SnO₂ nanoparticles and its photocatalytic activity of phenolsulfonphthalein dye. Spectrochim Acta A. 2015;145:176–80.

[21] Iravani S. Green synthesis of metal nanoparticles using plants. Green Chem. 2011;13:2638–50.

[22] Patete JM, Peng X, Koenigsmann C, Xu Y, Karnb B, Wong SS. Viable methodologies for the synthesis of high-quality nanostructures. Green Chem. 2011;13:482–519.

[23] Susan A, Mansor BA, Farideh N, Rosfarizan M. Green biosynthesis and characterization of zinc oxide nanoparticles using brown marine macroalga Sargassum muticum aqueous extract. Mater Lett. 2014;116:275–7.

[24] Kouvaris P, Andreas D, Vassilis Z, Dimitrios P, Sofia AT, Michailidis N. Green synthesis and characterization of silver nanoparticles produced using Arbutus unedo leaf extract. Mater Lett. 2012;76:18–20.

[25] Manukyan KV, Avetisyan AG, Shuck CE, Chatilyan HA, Rouvimov S, Kharatyan SL, et al. Nickel oxide reduction by hydrogen: kinetics and structural transformations. J Phys Chem C. 2015;119(28):16131–8.

[26] Bonomo M. Synthesis and characterization of NiO nanostructures: a review. J Nanopart Res. 2018;20:222.

[27] Tientong J, Garcia S, Thurber CR, Golden TD. Synthesis of nickel and nickel hydroxide nanopowder by simplified chemical reduction. J Nanotechnol. 2014;2014:1–6.

[28] Ghazal S, Akbari A, Hosseini HA, Sabouri Z, Forouzanfar F, Khatami M, et al. Sol-gel biosynthesis of nickel oxide nanoparticles using Cydonia oblonga extract and evaluation of their cytotoxicity and photocatalytic activities. J Mol Struct. 2020;1217:128378.

[29] Vardhan KH, Kumar PS, Panda RC. A review on heavy metal pollution, toxicity and remedial measures: Current trends and future perspectives. J Mol Liq. 2019;290:111197.

[30] Genchi G, Carocci A, Lauria G, Sinicropi MS, Catalano A. Nickel: Human Health and Environmental Toxicology. Int J Environ Res Public Health. 2020 Jan 21;17(3):679. doi: 10.3390/ijerph17030679.

[31] Venkitanarayanan K, Thakur S, Ricke SC, editors. Food safety in poultry meat production. Cham, Switzerland: Springer International Publishing; 2019.
[32] Saif S, Tahir A, Chen Y. Green synthesis of iron nanoparticles and their environmental applications and implications. Nanomaterials. 2016;6(11):209.

[33] Machado S, Pinto SL, Grosso JP, Nouws HPA, Albergaria JT, Delerue-Matos C. Green production of zero-valent iron nano-particles using tree leaf extracts. Sci Total Environ. 2013;445:1-8.

[34] Huang L, Weng X, Chen Z, Megharaj M, Naidu R. Green synthesis of iron nanoparticles by various tea extracts: comparative study of the reactivity. Spectrochim Acta A Mol Biomol Spectrosc. 2014;130:295-301.

[35] Luo F, Yang D, Chen Z, Megharaj M, Naidu R. One-step green synthesis of bimetallic Fe/Pd nanoparticles used to degrade Orange II. J Hazard Mater. 2016;303:145-53.

[36] Anstas PT, Warner JC. Green chemistry: theory and practice. New York: Oxford University Press, Inc; 1998.

[37] Ahmed S, Saif A, Chaudhry A, Ikram S. A review on biogenic synthesis of ZnO nanoparticles using plant extracts and microbes: a prospect towards green chemistry. J Photochem Photobiol B. 2017;166:272-84.

[38] Anthony KJP, Murugan M, Jeyaraj M, Gurunathan S. Multiple strategic approaches for green synthesis and application of silver and gold nanoparticles. In: Rai M, Posten M, editors. Green biosynthesis of nanoparticles: mechanisms and applications. Wallingford UK: CABI; 2013. p. 13-30.

[39] Moghaddam AB, Moniri M, Azizi S, Rahim RA, Ariff AB, Saad WZ, et al. Biosynthesis of ZnO Nanoparticles by a new Pichia kudriavzevii yeast strain and evaluation of their antimicrobial and antioxidant activities. Molecules. 2017;22:872-89.

[40] Chakravarty A, Ahmad I, Singh P, Ud Din Sheikh M, Aalam G, Sagadevan S, et al. Green synthesis of silver nanoparticles using fruits extracts of Syzygium cumini and their bioactivity. Chem Phys Lett. 2022;795:139493.

[41] Elumalai K, Velmurugan S. Green synthesis, characterization and antimicrobial activities of zinc oxide nanoparticles from the leaf extract of Azadirachta indica (L.). Appl Surf Sci. 2015;345:329-36.

[42] Ajitha B, Reddy YAK, Reddy PS. Green synthesis and characterization of silver nanoparticles using Lantana camara leaf extract. Mater Sci Eng C. 2015;49:373-81.

[43] Castillo-Henriquez L, Alfaro-Aguilar K, Ugalde-Álvarez J, Vega-Fernández L, Montes de Oca-Vásquez G, Vega-Baudrit JR. Green Synthesis of Gold and Silver Nanoparticles from Plant Extracts and Their Possible Applications as Antimicrobial Agents in the Agricultural Area. Nanomaterials. 2020;10:1763.

[44] Gour A, Jain NK. Advances in green synthesis of nanoparticles. Artif Cell Nanomed Biotechnol. 2019;47:844-51.

[45] Adil SF, Assal ME, Khan M, Al-Warthan A, Siddiqui MRH, Liz-Marzán LM. Biogenic synthesis of metallic nanoparticles and prospects toward green chemistry. Dalton Trans. 2015;44:9709-17.

[46] Zhang D, Ma X-L, Gu Y, Huang H, Zhang G-W. Green Synthesis of Metallic Nanoparticles and Their Potential Applications to Treat Cancer. Front Chem. 2020;8:799.

[47] Bouafia A, Laouini SE, Tedjani ML, Ali GA, Barhoum A. Green biosynthesis and physicochemical characterization of Fe3O4 nanoparticles using Punica granatum L. fruit peel extract for optoelectronic applications. Text Res J. 2022;92(15-16):2685-96.

[48] Dharmaraj D, Krishnamoorthy M, Rajendran K, Karuppiah K, Annamalai J, Durairaj KR, et al. Antibacterial and cytotoxic activities of biosynthesized silver oxide (Ag2O) nanoparticles using Bacillus paramycoides. J Drug Deliv Sci Technol. 2021;61:102111.

[49] Islam SN, Naqvi SMA, Parveen S, Ahmad A. Application of mycogenic silver/silver oxide nanoparticles in electrochemical glucose sensing; alongside their catalytic and antimicrobial activity. 3 Biotech. 2021;11:342.

[50] Mehata MS. Green route synthesis of silver nanoparticles using plants/ginger extracts with enhanced surface plasmon resonance and degradation of textile dye. Mater Sci Eng: B. 2021;273:115418.

[51] Chouke PB, Potbhare AK, Meshram NP, Rai MM, Dadure KM, Chaudhary K, et al. Bioinspired NiO nanospheres: Exploring in vitro toxicity using Bm-17 and L. rohita liver cells, DNA degradation, docking, and proposed vacuolization mechanism. ACS Omega. 2022;7(8):6869-84.

[52] Prabhu S, Thangadurai TD, Bharathy PV, Kalugasalam P. Synthesis and characterization of nickel oxide nanoparticles using Clitoria ternatea flower extract: Photocatalytic dye degradation under sunlight and antibacterial activity applications. Results Chem. 2022;4:100285.

[53] Slater TJ, Lewis EA, Haigh SJ. Energy dispersive X-ray tomography for 3D elemental mapping of individual nanoparticles. JoVE (J Visualized Exp). 2016;113:e52815.

[54] Goel R, Jha R, Ravikant C. Investigating the structural, electrochemical, and optical properties of p-type spherical nickel oxide (NiO) nanoparticles. J Phys Chem Solids. 2020;144:109488.

[55] Zorkipli NNM, Kaus NHM, Mohamad AA. Synthesis of NiO nanoparticles through sol-gel method. Procedia Chem. 2016;19:626-31.

[56] Barzinjy AA, Hamad SM, Aydin S, Ahmed MH, Hussain FH. Green and eco-friendly synthesis of Nickel oxide nanoparticles and its photocatalytic activity for methyl orange degradation. J Mater Sci: Mater Electron. 2020;31:11303-16.

[57] Chung IM, Abdul Rahuman A, Marimuthu S, Vishnu Kirthi A, Anbarasan K, Padmini P, et al. Green synthesis of copper nanoparticles using Eclipta prostrata leaves extract and their antioxidant and cytotoxic activities. Exp Therapeutic Med. 2017;14:18-24.

[58] Chatterjee AK, Sarkar RK, Chattopadhyay AP, Aich P, Chakraborty R, Basu T. A simple robust method for synthesis of metallic copper nanoparticles of high antibacterial potency against E. coli. Nanotechnology. 2012;23:085103.

[59] Makarov VV, Love AJ, Sinitsyna OV, Makarova SS, Yaminsky IV, Taliansky ME, et al. "Green" nanotechnologies: synthesis of metal nanoparticles using plants. Acta Nat. 2014;6:35-44.

[60] Ali K, Dwivedi S, Azam A, Saquib Q, Al-Said MS, Alkhedhairy AA, et al. Aloe vera extract functionalized zinc oxide nanoparticles as nanoantibiotics against multidrug resistant clinical bacterial isolates. J Colloid Interface Sci. 2016;472:145-56.

[61] Qian Y, Yao J, Russel M, Chen K, Wang X. Characterization of green synthesized nanoformulation (ZnO-A. vera) and their antibacterial activity against pathogens. Environ Toxicol Pharmacol. 2015;39:736-46.

[62] Jeetah R, Bhaw-Luximon A, Jhurry D. Nanopharmaceutics: phytochemical-based controlled or sustained drug-delivery systems for cancer treatment. J Biomed Nanotechnol. 2014;10:1810-40.

[63] Kumar S, Yadav A, Yadav M, Yadav JP. Effect of climate change on phytochemical diversity, total phenolic content and in vitro antioxidant activity of Aloe vera (L.) Burm.f. BMC Res Notes. 2017;10:60-71.

[64] Singh Y, Sodhi RS, Singh PP, Kaushal S. Biosynthesis of NiO nanoparticles using Spirogyra sp. cell-free extract and their
[32] Saif S, Tahir A, Chen Y. Green synthesis of iron nanoparticles and their environmental applications and implications. Nanomaterials. 2016;6(11):209.

[33] Machado S, Pinto SL, Grosso JP, Nouws HPA, Albergaria JT, Delerue-Matos C. Green production of zero-valent iron nano-particles using tree leaf extracts. Sci Total Environ. 2013;445:1-8.

[34] Huang L, Weng X, Chen Z, Megharaj M, Naidu R. Green synthesis of iron nanoparticles by various tea extracts: comparative study of the reactivity. Spectrochim Acta A Mol Biomol Spectrosc. 2014;130:295-301.

[35] Luo F, Yang D, Chen Z, Megharaj M, Naidu R. One-step green synthesis of bimetallic Fe/Pd nanoparticles used to degrade Orange II. J Hazard Mater. 2016;303:145-53.

[36] Anstas PT, Warner JC. Green chemistry: theory and practice. New York: Oxford University Press, Inc; 1998.

[37] Ahmed S, Saif A, Chaudhry A, Ikram S. A review on biogenic synthesis of ZnO nanoparticles using plant extracts and microbes: a prospect towards green chemistry. J Photochem Photobiol B. 2017;166:272-84.

[38] Anthony KJP, Murugan M, Jeyaraj M, Gurunathan S. Multiple strategic approaches for green synthesis and application of silver and gold nanoparticles. In: Rai M, Posten M, editors. Green biosynthesis of nanoparticles: mechanisms and applications. Wallingford UK: CABI; 2013. p. 13-30.

[39] Moghaddam AB, Moniri M, Azizi S, Rahim RA, Ariff AB, Saad WZ, et al. Biosynthesis of ZnO Nanoparticles by a new Pichia kudriavzevii yeast strain and evaluation of their antimicrobial and antioxidant activities. Molecules. 2017;22:872-89.

[40] Chakravarty A, Ahmad I, Singh P, Ud Din Sheikh M, Aalam G, Sagadevan S, et al. Green synthesis of silver nanoparticles using fruits extracts of Syzygium cumini and their bioactivity. Chem Phys Lett. 2022;795:139493.

[41] Elumalai K, Velmurugan S. Green synthesis, characterization and antimicrobial activities of zinc oxide nanoparticles from the leaf extract of Azadirachta indica (L.). Appl Surf Sci. 2015;345:329-36.

[42] Ajitha B, Reddy YAK, Reddy PS. Green synthesis and characterization of silver nanoparticles using Lantana camara leaf extract. Mater Sci Eng C. 2015;49:373-81.

[43] Castillo-Henriquez L, Alfaro-Aguilar K, Ugalde-Álvarez J, Vega-Fernández L, Montes de Oca-Vásquez G, Vega-Baudrit JR. Green Synthesis of Gold and Silver Nanoparticles from Plant Extracts and Their Possible Applications as Antimicrobial Agents in the Agricultural Area. Nanomaterials. 2020;10:1763.

[44] Gour A, Jain NK. Advances in green synthesis of nanoparticles. Artif Cell Nanomed Biotechnol. 2019;47:844-51.

[45] Adil SF, Assal ME, Khan M, Al-Warthan A, Siddiqui MRH, Liz-Marzán LM. Biogenic synthesis of metallic nanoparticles and prospects toward green chemistry. Dalton Trans. 2015;44:9709-17.

[46] Zhang D, Ma X-L, Gu Y, Huang H, Zhang G-W. Green Synthesis of Metallic Nanoparticles and Their Potential Applications to Treat Cancer. Front Chem. 2020;8:799.

[47] Bouafia A, Laouini SE, Tedjani ML, Ali GA, Barhoum A. Green biosynthesis and physicochemical characterization of Fe3O4 nanoparticles using Punica granatum L. fruit peel extract for optoelectronic applications. Text Res J. 2022;92(15-16):2685-96.

[48] Dharmaraj D, Krishnamoorthy M, Rajendran K, Karuppiah K, Annamalai J, Durairaj KR, et al. Antibacterial and cytotoxic activities of biosynthesized silver oxide (Ag2O) nanoparticles using Bacillus paramycoides. J Drug Deliv Sci Technol. 2021;61:102111.

[49] Islam SN, Naqvi SMA, Parveen S, Ahmad A. Application of mycogenic silver/silver oxide nanoparticles in electrochemical glucose sensing; alongside their catalytic and antimicrobial activity. 3 Biotech. 2021;11:342.

[50] Mehata MS. Green route synthesis of silver nanoparticles using plants/ginger extracts with enhanced surface plasmon resonance and degradation of textile dye. Mater Sci Eng: B. 2021;273:115418.

[51] Chouke PB, Potbhare AK, Meshram NP, Rai MM, Dadure KM, Chaudhary K, et al. Bioinspired NiO nanospheres: Exploring in vitro toxicity using Bm-17 and L. rohita liver cells, DNA degradation, docking, and proposed vacuolization mechanism. ACS Omega. 2022;7(8):6869-84.

[52] Prabhu S, Thangadurai TD, Bharathy PV, Kalugasalam P. Synthesis and characterization of nickel oxide nanoparticles using Clitoria ternatea flower extract: Photocatalytic dye degradation under sunlight and antibacterial activity applications. Results Chem. 2022;4:100285.

[53] Slater TJ, Lewis EA, Haigh SJ. Energy dispersive X-ray tomography for 3D elemental mapping of individual nanoparticles. JoVE (J Visualized Exp). 2016;113:e52815.

[54] Goel R, Jha R, Ravikant C. Investigating the structural, electrochemical, and optical properties of p-type spherical nickel oxide (NiO) nanoparticles. J Phys Chem Solids. 2020;144:109488.

[55] Zorkipli NNM, Kaus NHM, Mohamad AA. Synthesis of NiO nanoparticles through sol-gel method. Procedia Chem. 2016;19:626-31.

[56] Barzinjy AA, Hamad SM, Aydin S, Ahmed MH, Hussain FH. Green and eco-friendly synthesis of Nickel oxide nanoparticles and its photocatalytic activity for methyl orange degradation. J Mater Sci: Mater Electron. 2020;31:11303-16.

[57] Chung IM, Abdul Rahuman A, Marimuthu S, Vishnu Kirthi A, Anbarasan K, Padmini P, et al. Green synthesis of copper nanoparticles using Eclipta prostrata leaves extract and their antioxidant and cytotoxic activities. Exp Therapeutic Med. 2017;14:18-24.

[58] Chatterjee AK, Sarkar RK, Chattopadhyay AP, Aich P, Chakraborty R, Basu T. A simple robust method for synthesis of metallic copper nanoparticles of high antibacterial potency against E. coli. Nanotechnology. 2012;23:085103.

[59] Makarov VV, Love AJ, Sinitsyna OV, Makarova SS, Yaminsky IV, Taliansky ME, et al. "Green" nanotechnologies: synthesis of metal nanoparticles using plants. Acta Nat. 2014;6:35-44.

[60] Ali K, Dwivedi S, Azam A, Saquib Q, Al-Said MS, Alkhedhairy AA, et al. Aloe vera extract functionalized zinc oxide nanoparticles as nanoantibiotics against multidrug resistant clinical bacterial isolates. J Colloid Interface Sci. 2016;472:145-56.

[61] Qian Y, Yao J, Russel M, Chen K, Wang X. Characterization of green synthesized nanoformulation (ZnO-A. vera) and their antibacterial activity against pathogens. Environ Toxicol Pharmacol. 2015;39:736-46.

[62] Jeetah R, Bhaw-Luximon A, Jhurry D. Nanopharmaceutics: phytochemical-based controlled or sustained drug-delivery systems for cancer treatment. J Biomed Nanotechnol. 2014;10:1810-40.

[63] Kumar S, Yadav A, Yadav M, Yadav JP. Effect of climate change on phytochemical diversity, total phenolic content and in vitro antioxidant activity of Aloe vera (L.) Burm.f. BMC Res Notes. 2017;10:60-71.

[64] Singh Y, Sodhi RS, Singh PP, Kaushal S. Biosynthesis of NiO nanoparticles using Spirogyra sp. cell-free extract and their
potential biological applications. Mater Adv.
2022;3(12):4991-5000.

[65] Lovley DR, Stolz JF, Nord GL Jr., Phillips EJP. Anaerobic production of magnetite by a dissimilatory iron-reducing microorganism. Nature. 1987;330:252-4.

[66] Philipse AP, Maas D. Magnetic colloids from magnetotactic bacteria: chain formation and colloidal stability. Langmuir. 2002;18:9977-84.

[67] Karpagavinayagam P, Emi Princess Prasanna A, Vedhi C. Eco-friendly synthesis of nickel oxide nanoparticles using Avicennia Marina leaf extract: Morphological characterization and electrochemical application. Mater Today: Proc. 2022;48:136-42.

[68] Rashid IM, Salman SD, Mohammed AK, Mahdi YS. Green synthesis of nickle oxide nanoparticles for adsorption of dyes. Sains Malaysiana. 2022;51(2):533-46.

[69] Ahmad B, Khan MI, Naeem MA, Alhodaib A, Fatima M, Amami M, et al. Green synthesis of NiO nanoparticles using Aloe vera gel extract and evaluation of antimicrobial activity. Mater Chem Phys. 2022;288:126363.

[70] Ali T, Warsi MF, Zulfiqar S, Sami A, Ullah S, Rasheed A, et al. Green nickel/nickel oxide nanoparticles for prospective antibacterial and environmental remediation applications. Ceram Int. 2022;48:8331-40.

[71] Zhang Y, Mahdavi B, Mohammadhosseini M, Rezaei-Seresht E, Paydarfard S, Qorbani M, et al. Green synthesis of NiO nanoparticles using Calendula officinalis extract: Chemical characterization, antioxidant, cytotoxicity, and anti-esophageal carcinoma properties. Arab J Chem. 2021;14(5):103105.

[72] Khan SA, Shahid S, Ayaz A, Alkahtani J, Elshikh MS, Riaz T. Phytomolecules-coated NiO nanoparticles synthesis using abutilon indicum leaf extract: antioxidant, antibacterial, and anticancer activities. Int J Nanomed. 2021;16:1757-73.

[73] Iqbal A, Haq AU, Cerrón-Calle GA, Naqvi SA, Westerhoff P, Garcia-Segura S. Green synthesis of flower-shaped copper oxide and nickel oxide nanoparticles via capparis decidua leaf extract for synergic adsorption- photocatalytic degradation of pesticides. Catalysts. 2021;11:806.

[74] Ur S, Cr RK, Ms K, Betageri VS, Ms L, Veerapur R, et al. Biogenic Synthesis of NiO Nanoparticles Using Areca catechu Leaf Extract and Their Antidiabetic and Cytotoxic Effects. Molecules. 2021;26:2448.

[75] Boudiaf M, Messai Y, Bentouhami E, Schmutz M, Blanck C, Ruhlmann L, et al. Green synthesis of NiO nanoparticles using Nigella sativa extract and their enhanced electro-catalytic activity for 4-nitrophenol degradation. J Phys Chem Solids. 2021;153:110020.

[76] Feiona TA, Sabeena G, Bagavathy MS, Pushpalaksmi E, Jenson Samraj J, Annadurai G. Recent advances in the synthesis and characterization of nanoparticles: A green adeptness for photocatalytic and antibacterial activity. Nat Environ Pollut Technol. 2021;20(2):657-63.

[77] Uddin S, Safdar LB, Anwar S, Iqbal J, Laila S, Abbasi BA, et al. Green synthesis of nickel oxide nanoparticles from Berberis balochistanica stem for investigating Bioactivities. Molecules. 2021;26:1548.

[78] Noukelag SK, Mohamed HEA, Moussa B, Razanamahandry LC, Ntwampe SKO, Arendse CJ. Structural and Optical investigations of biosynthesised bunsenite NiO nanoparticles via an aqueous extract of Rosmarinus officinalis leaves. Mater Today Proc. 2021;36:245-50.

[79] Gebretinsae H, Welegergs G, Matinise N, Maaza M, Nuru ZY. Electrochemical study of Nickel Oxide (NiO) nanoparticles from cactus plant extract. MRS Adv. 2020;5:1095-102.

[80] Kumar MS, Soundarya TL, Nagaraju G, Raghu GK, Rekha ND, Alharthi FA, et al. Multifunctional applications (NiO) nanoparticles synthesised by facile green combustion method using Limonia acidissima natural fruit juice. Inorganica Chim Acta. 2021;515:120059.

[81] Haq S, Dildar S, Ali MB, Mezni A, Hedfi A, Shahzad MI, et al. Antimicrobial and antioxidant properties of biosynthesis of NiO nanoparticles using Raphanus sativus extract. Mater Res Express. 2021;8:055006.

[82] Sabouri Z, Akbari A, Hosseini HA, Khatami M, Darroudi M. Green-based bio-synthesis of Nickel Oxide nanoparticles in arabic gum and examination of their cytotoxicity, photocatalytic and antibacterial effects. Green Chem Lett Rev. 2021;14:404-14.

[83] Zhang Q, Xu S, Li Y, Ding P, Zhang Y, Zhao P. Supplementation of green-synthesized nickel oxide nanoparticles enhances biohydrogen production of Klebsilla sp. using lignocellulosic hydrolysate and elucidation of the regulatory mechanism. Res Sq. 2021. doi: 10.21203/rs.3.rs-314916/v1.

[84] Kumar MS, Soundarya TL, Nagaraju G, Raghu GK, Rekha ND, Alharthi FA, et al. Multifunctional applications of Nickel oxide (NiO) nanoparticles synthesized by facile green combustion method using Limonia acidissima natural fruit juice. Inorganica Chim Acta. 2021;515:120059.

[85] Lingaraju K, Raja Naika H, Nagabhushana H, Jayanna K, Devaraja S, Nagaraju G. Biosynthesis of Nickel oxide Nanoparticles from Euphorbia heterophylla (L.) and their biological application. Arab J Chem. 2020;13:4712-9.

[86] Iqbal J, Abbasi BA, Ahmad R, Mahmoodi M, Munir A, Zahra SA, et al. Phytogenic synthesis of nickel oxide nanoparticles (NiO) using fresh leaves extract of Rhamnus triquetra (Wall.) and investigation of its multiple in vitro biological potentials. Biomedicines. 2020;8:117.

[87] Habtemariam AB, Oumer M. Plant extract mediated synthesis of nickel oxide nanoparticles. Mater Int. 2020;2:205-9.

[88] Angel Ezhilarasi A, Judith Vijaya J, John Kennedy L, Kaviyarasu K. Green mediated NiO nano-rods using Phoenix dactylifera (Dates) extract for biomedical and environmental applications. Mater Chem Phys. 2020;241:122419.

[89] Ramesh R, Yamini V, John Sundaram S, Liakath Ali Khan F, Kaviyarasu K. Investigation of structural and optical properties of NiO nanoparticles mediated by Plectranthus amboinicus leaf extract. Mater Today: Proc. 2021;36:268-72.

[90] Olajire AA, Mohammed AA. Green synthesis of nickel oxide nanoparticles and studies of their photocatalytic activity in degradation of polyethylene films. Adv Powder Technol. 2020;31:211-8.

[91] Srihasam S, Thyagarajan K, Korivi M, Lebaka VR, Mallem SP. Phytogenic generation of NiO nanoparticles using stevia leaf extract and evaluation of their in-vitro antioxidant and Antimicrobial properties. Biomolecules. 2020;10:89.

[92] Ezhilarasi AA, Vijaya JJ, Kaviyarasu K, Zhang X, Kennedy LJ. Green synthesis of nickel oxide nanoparticles using Solanum trilobatum extract for cytotoxicity, antibacterial and photocatalytic studies. Surf Interfaces. 2020;20:100553.

[93] Priya A, Saminathan S, Balasundaram J. Green synthesis of NiO nanoparticles using Leucas Aspera and its antibacterial activity. Lett Appl NanoBioScience. 2020;9:1033-6.
potential biological applications. Mater Adv.
2022;3(12):4991-5000.

[65] Lovley DR, Stolz JF, Nord GL Jr., Phillips EJP. Anaerobic production of magnetite by a dissimilatory iron-reducing microorganism. Nature. 1987;330:252-4.

[66] Philipse AP, Maas D. Magnetic colloids from magnetotactic bacteria: chain formation and colloidal stability. Langmuir. 2002;18:9977-84.

[67] Karpagavinayagam P, Emi Princess Prasanna A, Vedhi C. Eco-friendly synthesis of nickel oxide nanoparticles using Avicennia Marina leaf extract: Morphological characterization and electrochemical application. Mater Today: Proc. 2022;48:136-42.

[68] Rashid IM, Salman SD, Mohammed AK, Mahdi YS. Green synthesis of nickle oxide nanoparticles for adsorption of dyes. Sains Malysiana. 2022;51(2):533-46.

[69] Ahmad B, Khan MI, Naeem MA, Alhodaib A, Fatima M, Amami M, et al. Green synthesis of NiO nanoparticles using Aloe vera gel extract and evaluation of antimicrobial activity. Mater Chem Phys. 2022;288:126363.

[70] Ali T, Warsi MF, Zulfiqar S, Sami A, Ullah S, Rasheed A, et al. Green nickel/nickel oxide nanoparticles for prospective antibacterial and environmental remediation applications. Ceram Int. 2022;48:8331-40.

[71] Zhang Y, Mahdavi B, Mohammadhosseini M, Rezaei-Seresht E, Paydarfard S, Qorbani M, et al. Green synthesis of NiO nanoparticles using Calendula officinalis extract: Chemical characterization, antioxidant, cytotoxicity, and anti-esophageal carcinoma properties. Arab J Chem. 2021;14(5):103105.

[72] Khan SA, Shahid S, Ayaz A, Alkahtani J, Elshikh MS, Riaz T. Phytomolecules-coated NiO nanoparticles synthesis using abutilon indicum leaf extract: antioxidant, antibacterial, and anticancer activities. Int J Nanomed. 2021;16:1757-73.

[73] Iqbal A, Haq AU, Cerrón-Calle GA, Naqvi SA, Westerhoff P, Garcia-Segura S. Green synthesis of flower-shaped copper oxide and nickel oxide nanoparticles via capparis decidua leaf extract for synergic adsorption- photocatalytic degradation of pesticides. Catalysts. 2021;11:806.

[74] Ur S, Cr RK, Ms K, Betageri VS, Ms L, Veerapur R, et al. Biogenic Synthesis of NiO Nanoparticles Using Areca catechu Leaf Extract and Their Antidiabetic and Cytotoxic Effects. Molecules. 2021;26:2448.

[75] Boudiaf M, Messai Y, Bentouhami E, Schmutz M, Blanck C, Ruhlmann L, et al. Green synthesis of NiO nanoparticles using Nigella sativa extract and their enhanced electro-catalytic activity for 4-nitrophenol degradation. J Phys Chem Solids. 2021;153:110020.

[76] Feiona TA, Sabeena G, Bagavathy MS, Pushpalaksmi E, Jenson Samraj J, Annadurai G. Recent advances in the synthesis and characterization of nanoparticles: A green adeptness for photocatalytic and antibacterial activity. Nat Environ Pollut Technol. 2021;20(2):657-63.

[77] Uddin S, Safdar LB, Anwar S, Iqbal J, Laila S, Abbasi BA, et al. Green synthesis of nickel oxide nanoparticles from Berberis balochistanica stem for investigating Bioactivities. Molecules. 2021;26:1548.

[78] Noukelag SK, Mohamed HEA, Moussa B, Razanamahandry LC, Ntwampe SKO, Arendse CJ. Structural and Optical investigations of biosynthesised bunsenite NiO nanoparticles via an aqueous extract of Rosmarinus officinalis leaves. Mater Today Proc. 2021;36:245-50.

[79] Gebretinsae H, Welegergs G, Matinise N, Maaza M, Nuru ZY. Electrochemical study of Nickel Oxide (NiO) nanoparticles from cactus plant extract. MRS Adv. 2020;5:1095-102.

[80] Kumar MS, Soundarya TL, Nagaraju G, Raghu GK, Rekha ND, Alharthi FA, et al. Multifunctional applications (NiO) nanoparticles synthesised by facile green combustion method using Limonia acidissima natural fruit juice. Inorganica Chim Acta. 2021;515:120059.

[81] Haq S, Dildar S, Ali MB, Mezni A, Hedfi A, Shahzad MI, et al. Antimicrobial and antioxidant properties of biosynthesis of NiO nanoparticles using Raphanus sativus extract. Mater Res Express. 2021;8:055006.

[82] Sabouri Z, Akbari A, Hosseini HA, Khatami M, Darroudi M. Green-based bio-synthesis of Nickel Oxide nanoparticles in arabic gum and examination of their cytotoxicity, photocatalytic and antibacterial effects. Green Chem Lett Rev. 2021;14:404-14.

[83] Zhang Q, Xu S, Li Y, Ding P, Zhang Y, Zhao P. Supplementation of green-synthesized nickel oxide nanoparticles enhances biohydrogen production of Klebsilla sp. using lignocellulosic hydrolysate and elucidation of the regulatory mechanism. Res Sq. 2021. doi: 10.21203/rs.3.rs-314916/v1.

[84] Kumar MS, Soundarya TL, Nagaraju G, Raghu GK, Rekha ND, Alharthi FA, et al. Multifunctional applications of Nickel oxide (NiO) nanoparticles synthesized by facile green combustion method using Limonia acidissima natural fruit juice. Inorganica Chim Acta. 2021;515:120059.

[85] Lingaraju K, Raja Naika H, Nagabhushana H, Jayanna K, Devaraja S, Nagaraju G. Biosynthesis of Nickel oxide Nanoparticles from Euphorbia heterophylla (L.) and their biological application. Arab J Chem. 2020;13:4712-9.

[86] Iqbal J, Abbasi BA, Ahmad R, Mahmoodi M, Munir A, Zahra SA, et al. Phytogenic synthesis of nickel oxide nanoparticles (NiO) using fresh leaves extract of Rhamnus triquetra (Wall.) and investigation of its multiple in vitro biological potentials. Biomedicines. 2020;8:117.

[87] Habtemariam AB, Oumer M. Plant extract mediated synthesis of nickel oxide nanoparticles. Mater Int. 2020;2:205-9.

[88] Angel Ezhilarasi A, Judith Vijaya J, John Kennedy L, Kaviyarasu K. Green mediated NiO nano-rods using Phoenix dactylifera (Dates) extract for biomedical and environmental applications. Mater Chem Phys. 2020;241:122419.

[89] Ramesh R, Yamini V, John Sundaram S, Liakath Ali Khan F, Kaviyarasu K. Investigation of structural and optical properties of NiO nanoparticles mediated by Plectranthus amboinicus leaf extract. Mater Today: Proc. 2021;36:268-72.

[90] Olajire AA, Mohammed AA. Green synthesis of nickel oxide nanoparticles and studies of their photocatalytic activity in degradation of polyethylene films. Adv Powder Technol. 2020;31:211-8.

[91] Srihasam S, Thyagarajan K, Korivi M, Lebaka VR, Mallem SP. Phytogenic generation of NiO nanoparticles using stevia leaf extract and evaluation of their in-vitro antioxidant and Antimicrobial properties. Biomolecules. 2020;10:89.

[92] Ezhilarasi AA, Vijaya JJ, Kaviyarasu K, Zhang X, Kennedy LJ. Green synthesis of nickel oxide nanoparticles using Solanum trilobatum extract for cytotoxicity, antibacterial and photocatalytic studies. Surf Interfaces. 2020;20:100553.

[93] Priya A, Saminathan S, Balasundaram J. Green synthesis of NiO nanoparticles using Leucas Aspera and its antibacterial activity. Lett Appl NanoBioScience. 2020;9:1033-6.
[94] Sheikh-Mohseni MH, Sedaghat S, Derakhshi P, Safekordi A. Green bio-synthesis of Ni/montmorillonite nanocomposite using extract of Allium jesdianum as the nano-catalyst for electrocatalytic oxidation of methanol. Chin J Chem Eng. 2020;28(10):2555-65.

[95] Haider A, Ijaz M, Ali S, Haider J, Imran M, Majeed H, et al. Green synthesized phytochemically (Zingiber officinale and allium sativum) reduced nickel oxide nanoparticles confirmed bactericidal and catalytic potential. Nanoscale Res Lett. 2020;15:1-11.

[96] Fariq A, Khan T, Yasmin A. Microbial synthesis of nanoparticles and their potential applications in biomedicine. J Appl Biomed. 2017;15:241-8.

[97] Castro L, Blázquez ML, González FG, Ballester A. Mechanism and applications of metal nanoparticles prepared by bio-mediated process. Rev Adv Sci Eng. 2014;3:199-216.

[98] Jang HD, Kim SK, Chang H, Choi J-H, Cho B-G, Jo EH, et al. Three-dimensional crumpled graphenebased platinum-gold alloy nanoparticle composites as superior electrocatalysts for direct methanol fuel cells. Carbon. 2015;93:869-77.

[99] Singh P, Kim Y-J, Zhang D, Yang D-C. Biological synthesis of nanoparticles from plants and microorganisms. Trends Biotechnol. 2016;34:588-99.

[100] Saravanan M, Barik SK, Mubarak Ali D, Prakash P, Pugazhendhi A. Synthesis of silver nanoparticles from bacillus brevis (ncim 2533) and their antibacterial activity against pathogenic bacteria. Microb Pathog. 2018;116:221-6.

[101] Buszewski B, Railean-Plugaru V, Pomastowski P, Rafińska K, Szultka-Młynska M, Golinska P, et al. Antimicrobial activity of biosilver nanoparticles produced by a novel streptacidiphilus durhamensis strain. J Microbiol Immunol Infect. 2018;51:45-54.

[102] Sanaeimehr Z, Javadi I, Namvar F. Antiangiogenic and antiapoptotic effects of green-synthesized zinc oxide nanoparticles using sargassum muticum algae extraction. Cancer Nanotechnol. 2018;9:1-16.

[103] He S, Zhang Y, Guo Z, Gu N. Biological synthesis of gold nano-wires using extract of rhodopseudomonas capsulata. BiotechnolProg. 2008;24:476-80.

[104] Li C, Zhou L, Yanq H, Lv R, Tian P, Li X, et al. Self-assembled exopolysaccharide nanoparticles for bioremediation and green synthesis of noble metal nanoparticles. ACS Appl Mater Interfaces. 2017;9:22808-18.

[105] Golmohammadi H, Morales-Narvaez E, Naghi T, Merkoci A. Nanocellulose in sensing and biosensing. Chem Mater. 2017;29:5426-46.

[106] Li X, Xu H, Chen Z-S, Chen G. Biosynthesis of nanoparticles by microorganisms and their applications. J Nanomater. 2011;2011:1-16.

[107] Das VL, Thomas R, Varghese RT, Soniya E, Mathew J, Radhakrishnan E. Extracellular synthesis of silver nanoparticles by the bacillus strain cs 11 isolated from industrialized area. 3 Biotech. 2014;4:121-6.

[108] Yadav A, Kon K, Kratosova G, Duran N, Ingle AP, Rai M. Fungi as an efficient mycosystem for the synthesis of metal nanoparticles: Progress and key aspects of research. Biotechnol Lett. 2015;37:2099-120.

[109] Al-Dhabi NA, Mohammed Ghilan A-K, Arasu MV. Characterization of silver nanomaterials derived from marine streptomyces sp. Al-dhabi-87 and its in vitro application against multidrug resistant and extended-spectrum beta-lactamase clinical pathogens. Nanomaterials. 2018;8:279.

[110] Marooufpour N, Alizadeh M, Hatami M, Lajayer BA. Biological synthesis of nanoparticles by different groups of bacteria. In Microbial Nanobionics. Cham, Switzerland: Springer; 2019. p. 63-85.

[111] Fernández-Llamosas H, Castro L, Blázquez ML, Díaz E, Carmona M. Speeding up bioproduction of selenium nanoparticles by using vibrio natriegens as microbial factory. Sci Rep. 2017;7:16046.

[112] Arokiyaraj S, Arasu MV, Vincent S, Prakash NU, Choi SH, Oh YK, et al. Rapid green synthesis of silver nanoparticles from Chrysanthemum indicum L and its antibacterial and cytotoxic effects: an in vitro study. Int J Nanomed. 2014;9:379-88.

[113] Basak G, Das D, Das N. Dual role of acidic diacetate sophorolipid as biostabilizer for ZnO nanoparticle synthesis and biofunctionalizing agent against Salmonella enterica and Candida albicans. J Microbiol Biotechnol. 2014;24(1):87-96.

[114] Jesudoss SK, Vijaya JJ, Selvam NC, Kombaiah K, Sivachidambaram M, Adinaveen T, et al. Effects of Ba doping on structural, morphological, optical, and photocatalytic properties of self-assembled ZnO nanospheres. Clean Technol Environ Policy. 2016;18(3):729-41.

[115] Stoimenov PK, Klinger RL, Marchin GL, Klabunde KJ. Metal oxide nanoparticles as bactericidal agents. Langmuir. 2002;18(17):6679-86.

[116] Kokkoris M, Trapalis CC, Kossionides S, Vlastou R, Nsouli B, Grötzschel R, et al. RBS and HIRBS studies of nanostructured AgSiO2 sol-gel thin coatings. Nucl Instrum Methods Phys Res Sect B Beam Interact Mater At. 2002;188(1-4):67-72.

[117] Lin W, Huang Y-w, Zhou X-D, Ma Y. Toxicity of cerium oxide nanoparticles in human lung cancer cells. Int J Toxicol. 2006;25(6):451-7.

[118] Kim SH, Lee HS, Ryu DS, Choi SJ, Lee DS. Antibacterial activity of silver-nanoparticles against Staphylococcus aureus and Escherichia coli. Korean J Microbiol Biotechnol. 2011;39(1):77-85.

[119] Ezhilarasi AA, Vijaya JJ, Kaviyarasu K, Kennedy LJ, Ramalingam RJ, Al-Lohedan HA. Green synthesis of NiO nanoparticles using Aegle marmelos leaf extract for the evaluation of in-vitro cytotoxicity, antibacterial and photocatalytic properties. J Photochem Photobiol B Biol. 2018;180:39-50.

[120] Elamin NY, Indumathi T, Kumar ER. Murraya koenigii mediated synthesis of cobalt doped NiO nanoparticles: evaluation of structural, optical properties and anti-bacterial activity. Phys E Low-dimens Syst Nanostruct. 2022;142:115295.

[121] Fu PP, Xia Q, Hwang HM, Ray PC, Yu H. Mechanisms of nanotoxicity: generation of reactive oxygen species. J Food Drug Anal. 2014;22(1):64-75.

[122] Shaikh S, Nazam N, Rizvi SM, Ahmad K, Baig MH, Lee EJ, et al. Mechanistic insights into the antimicrobial actions of metallic nanoparticles and their implications for multidrug resistance. Int J Mol Sci. 2019;20(10):2468.

[123] Al-Fa'ouri AM, Abu-Kharma MH, Awwad AM. Green synthesis of copper oxide nanoparticles using Bougainvillea leaves aqueous extract and antibacterial activity evaluation. Chem Int. 2021;7(3):155-62.

[124] Ahmad W, Bhatt SC, Verma M, Kumar V, Kim H. A review on current trends in the green synthesis of nickel oxide nanoparticles, characterizations, and their applications. Environ Nanotechnol Monit Manag. 2022;18:100674.

[125] Kumar PV, Pammi S, Shameem U. A Green approach for the synthesis of iron oxide nanoparticles by using roots of A.
[94] Sheikh-Mohseni MH, Sedaghat S, Derakhshi P, Safekordi A. Green bio-synthesis of Ni/montmorillonite nanocomposite using extract of Allium jesdianum as the nano-catalyst for electrocatalytic oxidation of methanol. Chin J Chem Eng. 2020;28(10):2555-65.

[95] Haider A, Ijaz M, Ali S, Haider J, Imran M, Majeed H, et al. Green synthesized phytochemically (Zingiber officinale and allium sativum) reduced nickel oxide nanoparticles confirmed bactericidal and catalytic potential. Nanoscale Res Lett. 2020;15:1-11.

[96] Fariq A, Khan T, Yasmin A. Microbial synthesis of nanoparticles and their potential applications in biomedicine. J Appl Biomed. 2017;15:241-8.

[97] Castro L, Blázquez ML, González FG, Ballester A. Mechanism and applications of metal nanoparticles prepared by bio-mediated process. Rev Adv Sci Eng. 2014;3:199-216.

[98] Jang HD, Kim SK, Chang H, Choi J-H, Cho B-G, Jo EH, et al. Three-dimensional crumpled graphenebased platinum-gold alloy nanoparticle composites as superior electrocatalysts for direct methanol fuel cells. Carbon. 2015;93:869-77.

[99] Singh P, Kim Y-J, Zhang D, Yang D-C. Biological synthesis of nanoparticles from plants and microorganisms. Trends Biotechnol. 2016;34:588-99.

[100] Saravanan M, Barik SK, Mubarak Ali D, Prakash P, Pugazhendhi A. Synthesis of silver nanoparticles from bacillus brevis (ncim 2533) and their antibacterial activity against pathogenic bacteria. Microb Pathog. 2018;116:221-6.

[101] Buszewski B, Railean-Plugaru V, Pomastowski P, Rafińska K, Szultka-Młynska M, Golinska P, et al. Antimicrobial activity of biosilver nanoparticles produced by a novel streptacidiphilus durhamensis strain. J Microbiol Immunol Infect. 2018;51:45-54.

[102] Sanaeimehr Z, Javadi I, Namvar F. Antiangiogenic and antiapoptotic effects of green-synthesized zinc oxide nanoparticles using sargassum muticum algae extraction. Cancer Nanotechnol. 2018;9:1-16.

[103] He S, Zhang Y, Guo Z, Gu N. Biological synthesis of gold nano-wires using extract of rhodopseudomonas capsulata. BiotechnolProg. 2008;24:476-80.

[104] Li C, Zhou L, Yanq H, Lv R, Tian P, Li X, et al. Self-assembled exopolysaccharide nanoparticles for bioremediation and green synthesis of noble metal nanoparticles. ACS Appl Mater Interfaces. 2017;9:22808-18.

[105] Golmohammadi H, Morales-Narvaez E, Naghi T, Merkoci A. Nanocellulose in sensing and biosensing. Chem Mater. 2017;29:5426-46.

[106] Li X, Xu H, Chen Z-S, Chen G. Biosynthesis of nanoparticles by microorganisms and their applications. J Nanomater. 2011;2011:1-16.

[107] Das VL, Thomas R, Varghese RT, Soniya E, Mathew J, Radhakrishnan E. Extracellular synthesis of silver nanoparticles by the bacillus strain cs 11 isolated from industrialized area. 3 Biotech. 2014;4:121-6.

[108] Yadav A, Kon K, Kratosova G, Duran N, Ingle AP, Rai M. Fungi as an efficient mycosystem for the synthesis of metal nanoparticles: Progress and key aspects of research. Biotechnol Lett. 2015;37:2099-120.

[109] Al-Dhabi NA, Mohammed Ghilan A-K, Arasu MV. Characterization of silver nanomaterials derived from marine streptomyces sp. Al-dhabi-87 and its in vitro application against multidrug resistant and extended-spectrum beta-lactamase clinical pathogens. Nanomaterials. 2018;8:279.

[110] Marooufpour N, Alizadeh M, Hatami M, Lajayer BA. Biological synthesis of nanoparticles by different groups of bacteria. In Microbial Nanobionics. Cham, Switzerland: Springer; 2019. p. 63-85.

[111] Fernández-Llamosas H, Castro L, Blázquez ML, Díaz E, Carmona M. Speeding up bioproduction of selenium nanoparticles by using vibrio natriegens as microbial factory. Sci Rep. 2017;7:16046.

[112] Arokiyaraj S, Arasu MV, Vincent S, Prakash NU, Choi SH, Oh YK, et al. Rapid green synthesis of silver nanoparticles from Chrysanthemum indicum L and its antibacterial and cytotoxic effects: an in vitro study. Int J Nanomed. 2014;9:379-88.

[113] Basak G, Das D, Das N. Dual role of acidic diacetate sophorolipid as biostabilizer for ZnO nanoparticle synthesis and biofunctionalizing agent against Salmonella enterica and Candida albicans. J Microbiol Biotechnol. 2014;24(1):87-96.

[114] Jesudoss SK, Vijaya JJ, Selvam NC, Kombaiah K, Sivachidambaram M, Adinaveen T, et al. Effects of Ba doping on structural, morphological, optical, and photocatalytic properties of self-assembled ZnO nanospheres. Clean Technol Environ Policy. 2016;18(3):729-41.

[115] Stoimenov PK, Klinger RL, Marchin GL, Klabunde KJ. Metal oxide nanoparticles as bactericidal agents. Langmuir. 2002;18(17):6679-86.

[116] Kokkoris M, Trapalis CC, Kossionides S, Vlastou R, Nsouli B, Grötzschel R, et al. RBS and HIRBS studies of nanostructured AgSiO2 sol-gel thin coatings. Nucl Instrum Methods Phys Res Sect B Beam Interact Mater At. 2002;188(1-4):67-72.

[117] Lin W, Huang Y-w, Zhou X-D, Ma Y. Toxicity of cerium oxide nanoparticles in human lung cancer cells. Int J Toxicol. 2006;25(6):451-7.

[118] Kim SH, Lee HS, Ryu DS, Choi SJ, Lee DS. Antibacterial activity of silver-nanoparticles against Staphylococcus aureus and Escherichia coli. Korean J Microbiol Biotechnol. 2011;39(1):77-85.

[119] Ezhilarasi AA, Vijaya JJ, Kaviyarasu K, Kennedy LJ, Ramalingam RJ, Al-Lohedan HA. Green synthesis of NiO nanoparticles using Aegle marmelos leaf extract for the evaluation of in-vitro cytotoxicity, antibacterial and photocatalytic properties. J Photochem Photobiol B Biol. 2018;180:39-50.

[120] Elamin NY, Indumathi T, Kumar ER. Murraya koenigii mediated synthesis of cobalt doped NiO nanoparticles: evaluation of structural, optical properties and anti-bacterial activity. Phys E Low-dimens Syst Nanostruct. 2022;142:115295.

[121] Fu PP, Xia Q, Hwang HM, Ray PC, Yu H. Mechanisms of nanotoxicity: generation of reactive oxygen species. J Food Drug Anal. 2014;22(1):64-75.

[122] Shaikh S, Nazam N, Rizvi SM, Ahmad K, Baig MH, Lee EJ, et al. Mechanistic insights into the antimicrobial actions of metallic nanoparticles and their implications for multidrug resistance. Int J Mol Sci. 2019;20(10):2468.

[123] Al-Fa'ouri AM, Abu-Kharma MH, Awwad AM. Green synthesis of copper oxide nanoparticles using Bougainvillea leaves aqueous extract and antibacterial activity evaluation. Chem Int. 2021;7(3):155-62.

[124] Ahmad W, Bhatt SC, Verma M, Kumar V, Kim H. A review on current trends in the green synthesis of nickel oxide nanoparticles, characterizations, and their applications. Environ Nanotechnol Monit Manag. 2022;18:100674.

[125] Kumar PV, Pammi S, Shameem U. A Green approach for the synthesis of iron oxide nanoparticles by using roots of A.
racemosus and its degradation of dye methyl orange. Int J Pharm. 2018;6:22-8.

[126] Pallela PN, Ummey S, Ruddaraju LK, Gadi S, Cherukuri CS, Barla S, et al. Antibacterial efficacy of green synthesized α-Fe₂O₃ nano-particles using Sida cordifolia plant extract. Heliyon. 2019;5(11):e02765.

[127] Agarwal H, Menon S, Kumar SV, Rajeshkumar S. Mechanistic study on antibacterial action of zinc oxide nanoparticles synthesized using green route. Chem Biol Interact. 2018;286:60-70.

[128] Shahzadi S, Zafar N, Sharif R. Antibacterial activity of metallic nanoparticles. Bacter Pathog Antibact Contr. 2018;51:292.

[129] Raffi M, Hussain F, Bhatti T, Akhter J, Hameed A, Hasan M. Antibacterial characterization of silver nanoparticles against E. coli ATCC-15224. J Mater Sci Technol. 2008;24:192-6.

[130] Baek Y-W, An Y-J. Microbial toxicity of metal oxide nanoparticles (CuO, NiO, ZnO, and Sb₂O₃) to Escherichia coli, Bacillus subtilis, and Streptococcus aureus. Sci Total Environ. 2011;409:1603-8.

[131] Pelgrift RY, Friedman AJ. Nanotechnology as a therapeutic tool to combat microbial resistance. Adv Drug Deliv Rev. 2013;65:1803-15.

[132] Nel A, Xia T, Madler L, Li N. Toxic potential of materials at the nanolevel. Nature. 2006;311:622-7.

[133] Diakowska D, Lewandowski A, Kopec W, Diakowski W, Chrzanowska T. Oxidative DNA damage and total antioxidant status in serum of patients with esophageal squamous cell carcinoma. Hepatogastroenterology. 2007;58:1701-4.

[134] Doak SH, Griffiths SM, Manshian B, Singh N, Williams PM, Brown AP. Confounding experimental considerations in Nanogenotoxicology. Mutagenesis. 2009;24:285-93.

[135] Roy R, Tripathi A, Das M, Dwivedi PD. Cytotoxicity and uptake of zinc oxide nanoparticles leading to enhanced inflammatory cytokines levels in murine macrophages: comparison with bulk zinc oxide. J Biomed Nanotechnol. 2011;7:110-1.

[136] Mazinanian N, Hedberg Y, Wallinder IO. Nickel release and surface characteristics of fine powders of nickel metal and nickel oxide in media of relevance for inhalation and dermal contact. Regul Toxicol Pharmacol. 2013;65:135-46.

[137] Hedberg Y, Hedberg J, Liu Y. Complexation-and ligand-induced metal release from 316L particles: importance of particle size and crystallographic structure. Biometals. 2011;24:1099-114.

[138] Pietruska JR, Liu X, Smith A, McNeil K, Weston P, Zhitkovich A, et al. Bioavailability, intracellular mobilization of nickel, and HIF-1 activation in human lung epithelial cells exposed to metallic nickel and nickel oxide nanoparticles. Toxicol Sci. 2011;124:138-48.

[139] Sabouri Z, Fereydouni N, Akbari A, Hosseini HA, Hashemzadeh A, Amiri MS, et al. Plant-based synthesis of NiO nanoparticles using salvia macrosiphon Boiss extract and examination of their water treatment. Rare Met. 2019;39:1-11.

[140] Kganyago P, Mahlaule-Glory LM, Mathipa MM, Ntsendwana B, Mketo N, Mbita Z, et al. Synthesis of NiO nanoparticles via a green route using Monsonia burkeana: The physical and biological properties. J Photochem Photobiolo B: Biol. 2018;182:18-26.

[141] Hosseinimehr SJ, Mahmoudzadeh A, Ahmadi A, Ashrafi SA, Shafaghati N, Hedayati N. The radioprotective effect of Zataria multiflora against genotoxicity induced by c irradiation in human blood lymphocytes. Cancer Biother Radiopharm. 2011;26:325-9.

[142] Chen M, Zhang Y, Huang B, Yang X, Wu Y, Liu B, et al. Evaluation of the antitumor activity by Ni nanoparticles with verbascoside. J Nanomater. 2013;2013:1-6.

[143] Rameshthangam P, Chitra JP. Synergistic anticancer effect of green synthesized nickel nanoparticles and quercetin extracted from Ocimum sanctum leaf extract. J Mater Sci Technol. 2018;34:508-22.

[144] Housein Z, Kareem TS, Salihi A. In vitro anticancer activity of hydrogen sulfide and nitric oxide alongside nickel nanoparticle and novel mutations in their genes in CRC patients. Sci Rep. 2021;11:2536.

[145] Madhu G, Biju V. Nanostructured amorphous nickel oxide with enhanced antioxidant activity. J Alloy Compd. 2015;637:62-9.

[146] Chen JH, Ho CT. Antioxidant activities of caffeic acid and its related hydroxycinnamic acid compounds. J Agric Food Chem. 1997;45(7):2374-8.
racemosus and its degradation of dye methyl orange. Int J Pharm. 2018;6:22-8.

[126] Pallela PN, Ummey S, Ruddaraju LK, Gadi S, Cherukuri CS, Barla S, et al. Antibacterial efficacy of green synthesized α-Fe₂O₃ nano-particles using Sida cordifolia plant extract. Heliyon. 2019;5(11):e02765.

[127] Agarwal H, Menon S, Kumar SV, Rajeshkumar S. Mechanistic study on antibacterial action of zinc oxide nanoparticles synthesized using green route. Chem Biol Interact. 2018;286:60-70.

[128] Shahzadi S, Zafar N, Sharif R. Antibacterial activity of metallic nanoparticles. Bacter Pathog Antibact Contr. 2018;51:292.

[129] Raffi M, Hussain F, Bhatti T, Akhter J, Hameed A, Hasan M. Antibacterial characterization of silver nanoparticles against E. coli ATCC-15224. J Mater Sci Technol. 2008;24:192-6.

[130] Baek Y-W, An Y-J. Microbial toxicity of metal oxide nanoparticles (CuO, NiO, ZnO, and Sb₂O₃) to Escherichia coli, Bacillus subtilis, and Streptococcus aureus. Sci Total Environ. 2011;409:1603-8.

[131] Pelgrift RY, Friedman AJ. Nanotechnology as a therapeutic tool to combat microbial resistance. Adv Drug Deliv Rev. 2013;65:1803-15.

[132] Nel A, Xia T, Madler L, Li N. Toxic potential of materials at the nanolevel. Nature. 2006;311:622-7.

[133] Diakowska D, Lewandowski A, Kopec W, Diakowski W, Chrzanowska T. Oxidative DNA damage and total antioxidant status in serum of patients with esophageal squamous cell carcinoma. Hepatogastroenterology. 2007;58:1701-4.

[134] Doak SH, Griffiths SM, Manshian B, Singh N, Williams PM, Brown AP. Confounding experimental considerations in Nanogenotoxicology. Mutagenesis. 2009;24:285-93.

[135] Roy R, Tripathi A, Das M, Dwivedi PD. Cytotoxicity and uptake of zinc oxide nanoparticles leading to enhanced inflammatory cytokines levels in murine macrophages: comparison with bulk zinc oxide. J Biomed Nanotechnol. 2011;7:110-1.

[136] Mazinanian N, Hedberg Y, Wallinder IO. Nickel release and surface characteristics of fine powders of nickel metal and nickel oxide in media of relevance for inhalation and dermal contact. Regul Toxicol Pharmacol. 2013;65:135-46.

[137] Hedberg Y, Hedberg J, Liu Y. Complexation-and ligand-induced metal release from 316L particles: importance of particle size and crystallographic structure. Biometals. 2011;24:1099-114.

[138] Pietruska JR, Liu X, Smith A, McNeil K, Weston P, Zhitkovich A, et al. Bioavailability, intracellular mobilization of nickel, and HIF-1 activation in human lung epithelial cells exposed to metallic nickel and nickel oxide nanoparticles. Toxicol Sci. 2011;124:138-48.

[139] Sabouri Z, Fereydouni N, Akbari A, Hosseini HA, Hashemzadeh A, Amiri MS, et al. Plant-based synthesis of NiO nanoparticles using salvia macrosiphon Boiss extract and examination of their water treatment. Rare Met. 2019;39:1-11.

[140] Kganyago P, Mahlaule-Glory LM, Mathipa MM, Ntsendwana B, Mketo N, Mbita Z, et al. Synthesis of NiO nanoparticles via a green route using Monsonia burkeana: The physical and biological properties. J Photochem Photobiolo B: Biol. 2018;182:18-26.

[141] Hosseinimehr SJ, Mahmoudzadeh A, Ahmadi A, Ashrafi SA, Shafaghati N, Hedayati N. The radioprotective effect of Zataria multiflora against genotoxicity induced by c irradiation in human blood lymphocytes. Cancer Biother Radiopharm. 2011;26:325-9.

[142] Chen M, Zhang Y, Huang B, Yang X, Wu Y, Liu B, et al. Evaluation of the antitumor activity by Ni nanoparticles with verbascoside. J Nanomater. 2013;2013:1-6.

[143] Rameshthangam P, Chitra JP. Synergistic anticancer effect of green synthesized nickel nanoparticles and quercetin extracted from Ocimum sanctum leaf extract. J Mater Sci Technol. 2018;34:508-22.

[144] Housein Z, Kareem TS, Salihi A. In vitro anticancer activity of hydrogen sulfide and nitric oxide alongside nickel nanoparticle and novel mutations in their genes in CRC patients. Sci Rep. 2021;11:2536.

[145] Madhu G, Biju V. Nanostructured amorphous nickel oxide with enhanced antioxidant activity. J Alloy Compd. 2015;637:62-9.

[146] Chen JH, Ho CT. Antioxidant activities of caffeic acid and its related hydroxycinnamic acid compounds. J Agric Food Chem. 1997;45(7):2374-8.