# Exploitation of Antimicrobial Nanoparticles and Their Applications in Biomedical Engineering
## 2 Nanomaterials
### Nanomaterials with Antimicrobial Properties
#### 2.3.1 Mono-Metallic Nanoparticles
pyogenes_, ampicillin-resistant _E. coli_ 0157:H7 and multidrug-resistant _P. aeruginosa_. On average, the MIC was found to be 79.4 nM, which was slightly higher than the MIC for drug-susceptible species (71.5 nM) [81]. Similarly, [PERSON] et al. found Ag NPs derived from _Phyllanthus amarus_ were antimicrobials effective against multidrug-resistant _P. aeruginosa_, with MIC values of 6.25-12.5 ug/mL, which are comparable to antibiotic concentrations towards the susceptible strains. [82]  
Despite Cu being an essential trace element in most organisms, excessive concentrations of exogenous Cu can be toxic [83]. In addition, Cu NPs have a lower economic cost and are known to have a wider microbial inhibition range than Ag NPs [84; 85]. Although, in some cases, higher Cu NPs concentrations were required to inhibit the target microbes, whereas when the same Ag NPs concentration was employed, it would show zero inhibitory effect [85]. A good example can be seen in [PERSON]'s study. No inhibitory effect was observed when 0.25 w/v% of Ag NPs was incubated with _S. aureus_, whilst at the same Cu NPs concentration, >99.5% microbial reduction was detected. Currently, three widely recognized antimicrobial mechanisms of Cu have been proposed amongst other numerous and complex mechanisms. First, the redox activity of the Cu (as well as Fe and Zn) ion catalysis the Haber-Weiss and Fenton reactions by shuttling between cupric ions (Cu\({}^{2+}\)) and cuprous ions (Cu\({}^{+}\)):  
\[Cu^{+}+H_{2}O_{2}+O_{2}^{-}\to O_{2}+Cu^{2+}+OH^{-}+\bullet OH\left(\text{ [PERSON]}-\text{[PERSON] reaction}\right)\]  
\[Cu^{+}+H_{2}O_{2}\to Cu^{2+}+OH^{-}+\bullet OH\left(\text{[PERSON] reaction}\right)\]  
In such a reaction, ROS and hydroxyl free radicals are formed, which can damage a range of cellular molecules, causing mutations in DNA [86]. In addition, Cu\({}^{+}\)/Cu\({}^{2+}\) ions can easily combine with sulphur-, nitrogen- or oxygen-containing functional groups to form organometallic complexes, resulting in defects in the conformational structure of nucleic acids and proteins [84]. Lastly, Cu\({}^{+}\)/Cu\({}^{2+}\) ions may also compete with non-Cu metal ions for important binding sites on proteins leading to reduced cellular functions [83]. Taking the inhibition of _E. coli_ as an example, excess Cu leads to a disintegration of iron-sulphur clusters, which are essential in dehydatase enzymes, leading to the inability of _E. coli_ to biosynthesize amino acids [87]. A separate research demonstrated that Cu NPs suspensions with a particle size of 100 nm at concentrations 33.4 and 28.2 ug/mL, respectively, reduced 90% populations of _E. coli_ and _B. subtilis_, whilst complete inhibitions of both bacteria were observed at doses over 60 ug/mL [88]. The MIC test was also carried out by placing nanoparticle-impregnated filter paper on agar plates. The MIC of Cu NPs for _E. coli_ was 140-280 ug/mL, whilst that for _S. aureus_ was 140 ug/mL [89]. In another study, [PERSON] et al. stated Cu-chitosan nanoparticles with a size of 2 to 350 nm can inhibit microorganisms including _S. aureus_, _B. subtilis_, _P. aeruginosa_, _S. choleraeusus_ and _Candidata albicans_[90]. It is known that Cu NPs can easily undergo oxidation in the presence of air/water. However, their oxidised intermediate (Cuprous oxide Cu\({}_{2}\)O) and product (Copper oxide CuO) are both known to possess antimicrobial activities that are effective against a range of pathogens, such as _Klebsiella pneumoniae, P. aeruginosa_, _S. parathyroid_ and _Shigeella_ strains, in a similar way to Cu NPs [90]. For instance, [PERSON] et al. stated CuO NPs can cross through the bacterial cell membrane and then damage the vital enzymes of bacteria to inhibit cells [91]. A study was performed by [PERSON] et al., where ultra-fine CuO NPs (10 nm) were prepared using a patented thermal plasma technology (Figure 2).