## 3 Results
### Nanoparticles for Colorectal Cancer Treatment
(2020) used a combination of doxorubicin (DOX) and aspirin together with siRNA-Bel2 co-administered in the same nanoformulation. Within this treatment, the simultaneous administration of DOX, aspirin and siRNA, at an effective concentration of 10 \(\upmu\)g/mL overall, achieved greater in vitro cell viability decline in cancer lines compared to the individual drugs. Furthermore, in vitro cellular uptake of the co-therapy improved 6-fold compared to the control, and G2/M arrest was higher in the synergistic therapy 2.5- and 3.6-fold over the individual drugs ([PERSON] et al., 2021). Meanwhile, [PERSON] et al. (2022) used paclitaxel as a co-therapy with siRNA against PD-L1, with the aim of inducing anti-tumor immunity. This study achieved a 45% reduction in cell viability in the synergic treatment compared to the nanoparticle alone. Also, in an in vivo xenograft model, the therapy induced a strong antitumor immunity with synergic treatment with a 66% reduction in tumor volume compared to the treatment with the chemotherapeutic agent alone ([PERSON] et al., 2021). Another study performed by [PERSON] et al. (2023) used the FuOXP (combination of 5-FU and OXA) prodrug encapsulated in an amphiphilic polymer (PMBOP), with a 1-octadecine lipid motif as a nanocarrier, with a hydrophobic core and surface coating and a mixture of chondro sulfate (natural ligand for CD44) and PEG (polyethylene glycol). This system co-delivers an siRNA against Xkr8, which is associated with tumor immunosuppression. This strategy achieved a 17% increase in caspase-3 levels compared with the full treatment and produced an increase of 20% in annexin V levels compared with the prodrug treatment. The in vivo results were also interesting, producing a drastic inhibition of tumoral growth with a 15% decrease in tumor volume with the full treatment in contrast with the siRNA alone ([PERSON] et al., 2021). Another study performed by [PERSON] et al. (2022) encapsulated regorafenib and quercetin separately through a biodegradable polymeric hybrid nanoparticle, constructed from mPEG-PCL and cationic lipid DDAB, and a shell coated with siRNA specific against a5B1. The NP treatment achieved a 20% and 55% decrease in the IC\({}_{50}\) compared to the drugs regorafenib and quercetin, respectively, demonstrating the in vitro synergistic potential of these nanoplatforms ([PERSON] et al., 2021). The last study, carried out by [PERSON] et al. (2020), used camptothecin, a topoisomerase I inhibitor, in simultaneous administration with a plasmid encoding for a specific shRNA against survivin as a synergistic therapy element, both encapsulated in the same NP. This strategy showed an 80% decrease in cell viability with full synergistic therapy, twice that achieved with the free drug (40%). Moreover, the mean final tumor burden volume of the synergistic treatment was reduced by 78.6% compared to over 40% with the no-surface-aptamer treatment and compared with the treatment with only the free drug [39]. For the treatment of colorectal cancer, many different chemotherapeutics and siRNA gene-s Silencing targets have been used, some of which have been reported in this systematic review. We can highlight the use of more conventional chemotherapeutics such as sorafenib, which is widely used to stop the spread of cancer cells, or newer drugs such as Cu2+ ions, which catalyze reactions with glutathione, converting H2O2 to -OH, generating a toxic response in tumor tissue. Among the gene targets silenced by siRNA, we can highlight CCAT1 or IDO1, both linked to molecular pathways involved in cell proliferation and chemoresistance. In each of the articles reviewed, strong in vitro and in vivo results were observed, significantly reducing cell viability and migration, reducing tumor volume compared to the administration of the individual treatments and even modifying the immunogenic microenvironment of the tumor. Each of these articles presents a potential preclinical therapy for the treatment of this type of neoplasm (Table 1).