## 3 Results
### Nanoparticles for Liver Cancer Treatment
The in vivo results showed a 68.33% tumoral volume reduction in vivo at the end of treatment compared to the synergistic therapy at half the concentration [46]. Furthermore, the study carried out by [PERSON] et al. (2020) employed cytoplasmic enzyme-degradable porous biological nanospheres with hydrophobic cavity using RNA as a building block and cyclodextrin to load sorafenibb and siRNA against EpCAM as a combination therapy. This study achieved a general reduction in cell viability with 90% compared to the untreated cells. In addition, the apoptosis rate increased to almost 20% compared to the free drug. In in vivo assays, the NP produced a 3-fold decrease in the tumor volume compared to the treatment using the nanoparticle and the aptamer alone [47]. In addition, [PERSON] et al. (2019), developed pH-sensitive lipid nanoparticles modified with a SP94-targeted peptide for liver cancer cells loaded with siMK and sorafenibb (SOR) as combined therapy. In this study, the IC50 for SOR + MK-siRNA decreased to 5 \(\pm\) 1.50 \(\upmu\)M, lower compared to the IC50 obtained with control SOR + siRNA at 9 \(\pm\) 2.20 and with gene silencing alone at 17 \(\pm\) 2.60 \(\upmu\)M [48]. [PERSON] et al. (2022) encapsulated a combination of sorafenibb and sunitinib through PVA-emulsified polymeric PLGA nanoparticles, co-loaded with siAFP as combination therapy against hepatocellular carcinoma. With this strategy, the cell viability with the complete combination therapy with sorafenibb 2.5 \(\upmu\)M decreased to 39.29 \(\pm\) 2.72%, whereas it decreased to 44.04 \(\pm\) 3.05% when combined with 5.0 \(\upmu\)M sunitinibb. Furthermore, caspase 3/7 activity increased by up to 300% with sunitinibb therapy and 200% with sorafenibb 5.0 \(\upmu\)M compared to no increase with sorafenibb at 2.5 \(\upmu\)M [49]. Other studies used cisplatin as chemotherapy encapsulated in its nanoparticles. [PERSON] et al. (2023) used a metal-organic framework nanocarrier, with a nuclear localization sequence (NLS) as the core and A54 peptide on the shell, coloaded with NOR1 shRNA. These NPs achieved a decrease in cancer cell viability of cisplatin-resistant cells of 90% in contrast to the 70% achieved with the free drug at the highest possible concentration. In the in vivo results, the group treated with the synergistic strategy showed inhibited tumor growth with an inhibition rate of 75 \(\pm\) 5% [50]. Meanwhile, [PERSON] et al. (2019) developed calcium phosphate nanoparticles with an asymmetric lipid bilayer coating loaded with cisplatin and siBmi-1 as antitumor therapy. The combined treatment induced a 20% increase in cell death compared to the free drug. In the in vivo xenograft model, the group treated with the synergistic therapy achieved the greatest inhibition of tumor growth with a final volume of 380.62 \(\pm\) 100.34 mm3 in contrast to 1271.69 \(\pm\) 59.69 mm3 for siRNA therapy [51]. [PERSON] et al. (2019) employed arsenic trioxide as a primary drug in Zinc arsenite NPs involved in a SiO\({}_{2}\) matrix to co-deliver siRNA against SHP-1. These NPs promotedapoptosis and significantly inhibit proliferation, migration, and invasion of tumor liver cells compared to the free drugs. With this strategy, the apoptosis was increased by 39% compared to chemotherapeutic alone. In the in vivo assay, the synergistic therapy inhibited tumor growth 2.2-fold and metastasis 3.5-fold compared with individual therapies [52]. Another chemotherapeutic drug employed was Adriamycin. [PERSON] et al. (2020) employed NPs co-loaded with siRNA against T-type Ca\({}^{2+}\) channels and Adriamycin, with the objective of decreasing intracellular Ca\({}^{2+}\) concentration and increasing chemosensitivity to Adriamycin. This study achieved an 80% cell viability decrease using synergistic therapy, increasing the cytotoxic potential compared with the NP encapsulating siRNA alone. In a xenograft model, the combined therapy produced a 60% inhibition in the tumor volume compared with the NP-siRNA that did not encapsulate the drug [53].