## 3 Results
### Nanoparticles for Colorectal Cancer Treatment
With this treatment, the IC\({}_{50}\) of the analyzed cell lines decreased by 67% with the synergistic complete therapy (5.7 \(\pm\) 1.7 \(\upmu\)M) compared to treatments without digitoxin (8.4 \(\pm\) 4.4 \(\upmu\)M). Furthermore, the survival of the mice treated with the synergistic therapy was better (20-24 more days), reducing the overall toxicity and increasing the immunogenicity, reducing the macrophage polarization by 30% [28]. In addition, [PERSON] et al. (2022) employed cationic liposomes, carrying siRNA against COL1A1 pro-\(\upalpha\) 1 chains of type I collagen of the extracellular matrix associated with poor prognosis in cancer development. The combination with the drugs oxaliplatin and 5-fluorofluarcil, co-incorporated after treatment with free-form siRNA, enhanced the antitumor effect of chemotherapy drugs and reversed chemoresistance. The inhibition of COL1A1 was better in the synergic treatment compared to the individual one. Furthermore, the authors observed a 5-fold and 3-fold IC\({}_{50}\) reduction with the synergic treatment compared to free 5-FU and OXA, respectively [29]. It is also worth highlighting the study carried out by [PERSON] et al. (2023) that employed a polymeric nanocomposite, loaded with siRNA against CCAT1 and Fru. Fru is the vascular endothelial growth factor receptor inhibitor, and it is used as a chemotherapeutic to inhibit epithelial-mesenchymal transition and increase drug chemosensitivity to exert antitumor and antiangiogenic effects. With this treatment, the co-loaded nanocomposite reduced the cell migration and viability ratio to almost half that of the untreated control and 20-30% that of the individualized treatments. Tumor volume was reduced by almost 1500 mm\({}^{3}\)[30]. Two of the studies analyzed incorporated doxorubicin (DOX) simultaneously with siRNA in the same nanovector. [PERSON] et al. (2023) used poly (lactic-coglycyclic acid) nanoemulsion, targeting cancer-associated fibroblasts via N-cadherin capped aptamer (NC3S) and carrying siRNA against HGF (Hepatocyte growth factor) to facilitate drug entry into the CAF-induced tumor microenvironment and regulate it [31]. The clonogenicity with this treatment was reduced by up to 200% compared to the untreated control, and the in vivotumor weight was reduced by up to almost 50% and tumoral volume to 75% with the complete treatment compared to the individual treatments. In addition, the study carried out by [PERSON] et al. (2021) employed chitosan lactate nanoparticles functionalized by the HIV-1-derived TAT peptide, which greatly increases the rate of cell penetration, and hyaluronate (linkage to CD44). This treatment reduced the side effects of DOX, stimulated anti-tumor immune responses and reduced the DOX IC\({}_{50}\) from 1097 to 451 nM. In in vivo assays, the tumor growth was reduced by 200% in the NP compared with the chemotherapeutic, with increased granzyme B, IFN-\(\gamma\), and IL-17 secretion and decreased IL-4 and IL-10 levels ([PERSON] et al., 2021). In addition, [PERSON] et al. (2021) encapsulated docetaxel combined with RelA siRNA treatment in cyclodextrin nanoparticles PEGylated and linked to a target of the folate receptor. In this study, a 95% cytotoxicity in tumor cell viability was achieved with the synergistic treatment in vitro and a 75% reduction in tumor volume between the synergic full treatment and the individual chemotherapeutic agent and siRNA ([PERSON] et al., 2021). On the other hand, [PERSON] et al. (2020) produced NPs encapsulating Cu\({}^{2+}\) ions, which catalyze reactions with glutathione, converting H\({}_{2}\)O\({}_{2}\) to -OH. In addition, they encapsulated siRNA against VEGF (siVEGF). The combined therapy increased the survival rate of mice with xenografts to 80% after 40 days of treatment, 55% more than the best result with individualized therapies without gene silencing. The CD4\({}^{+}\) and CD8\({}^{+}\) T-cell population increased by up to 5-10% compared to incomplete therapy without gene silencing ([PERSON] et al., 2021). [PERSON] et al.