## 3 Results
### Silver Nanoparticles  
Of the eight articles that used silver nanoparticles loaded with antitumor biomolecules, seven were in vitro cell culture studies [29; 30; 31; 32; 33; 34; 35] and one was an in vivo study with Wistar rats [23]. In each of these studies, the action of the extract alone was studied in comparison with the compound loaded in NPs. As can be seen from the results in Table 1, the IC\({}_{50}\) values obtained were lower in the nanoparticle treatments containing encapsulated extracts compared to the use of free extracts. Additionally, the studies by [PERSON] et al. (2021) and [PERSON] et al. (2021) showed that the cytotoxicity effect exerted by these silver nanoformulations only occurred in tumor lines, while healthy cells were resistant to the treatment as these silver nanoformulations did not induce any type of death process such as apoptosis [23; 31]. Thus, in the different tests that were carried out, NPs were loaded with a wide range of compounds extracted from different plant species, such as Moringa oleifera, Rosa indica and Vitex negundo. [PERSON] et al. (2021) examined the antitumor activity of _Moringa oleifera_ by obtaining an aqueous extract with 10% methanol from its leaves. This test was carried out in vivo on Wistar rats after promoting the development of dysplasia in their intestinal epithelium using azoxymethane (AOM). The encapsulation of the extract in silver nanoformulations obtained IC\({}_{50}\) values similar to the free extract, although those rats treated with these silver nanoformulations showed a decrease in the levels of carcinoembryonic antigen (CEA), Ca19.9 and inflammation markers. This effect is believed to be due to the presence of antioxidant polyphenols in the nano-extract, which could confer protection from oxidative damage by ROS. It also led to an increase in the levels of ROS detoxification enzymes, which were similar in the mice treated with the nano-extract compared to those of the control group without tumor. In addition, APC and TP53 levels decreased to normal values [23]. [PERSON] et al. (2021) created extracts from the leaves and skin of the fruits of _Ammonia muricata_. These extracts were tested on several CRC lines, such as MCF-7, MDA-MB-468 and HCT-116, showing a decrease in IC\({}_{50}\) values from 2004 to 404.8 \(\upmu\)g/mL in the extract from leaves, and a reduction from 1285 to 309.3 \(\upmu\)g/mL in the fruit skin extracts when encapsulated in iron nanoparticles. The enhanced cytotoxic effect could be due to the release of ions from nanoparticles, which are capable of activating signaling cascades, releasing calcium ions, and producing ROS damage at the mitochondrial level, thus increasing the cytotoxic effect generated by the extract itself [31]. On the other hand, [PERSON] et al. (2020) created extracts of _Putranjiva roxburghii_ (PJ) seeds that were subsequently encapsulated in iron NPs (PJ-SNPs). The results showed that the IC\({}_{50}\) of these nanoparticles (0.54 \(\upmu\)g/mL) was lower when compared to the free extract in this cell line (6 \(\upmu\)g/mL), which showed a better effect through an increase in apoptosis induction [29]. [PERSON] et al. (2020) evaluated the antitumor activity of _Caeslipinia pulcherrima_ and five types of extracts were obtained, one aqueous extract and four extracts from solvents (methanol, ethyl acetate, petroleum ether and chloroform). When comparing these extracts, it was observed that the aqueous extract presented the best antitumor activity, with  
Figure 3: Representative schematic of the synthesis material of the nanoformulations included in this systematic review. an IC\({}_{50}\) of 18.7 \(\upmu\)g/mL, compared to the extracts obtained from the solvents, whose IC\({}_{50}\) was 51, 72, 69.3 and 77 \(\upmu\)g/mL, respectively. Moreover, the encapsulation of the aqueous extract in a nanoformulation led to a decrease in IC\({}_{50}\) up to 3.8 \(\upmu\)g/mL, with encapsulation improving the effect of all the extracts tested on the HCT-116 cell line [30].