## 3 Results
### Nanoparticles for Liver Cancer Treatment  
Most of the studies included the chemotherapeutic DOX in conjunction with siRNA, such as the one carried out by [PERSON] et al. (2019) that employed DSPE-PEG-PEI nanoparticles, with glycyrrhetic acid-modified hyaluronic acid, to carry siRNA against Bcl-2. This study achieved a decrease in Bcl2 protein expression with the combination therapy. In addition, an in vivo study performed in mice with the synergistic RNAip/DOX/GH-DPP treatment produced a reduction in the tumor volume by 90% compared with the free drug [40]. On the other hand, [PERSON] et al. (2022) employed a hydrophobic core-shell nanoparticle loaded with DOX and siTOX to increase CD8\({}^{+}\) T-cell infiltration and achieve tumor inhibition. The treatment achieved a 17% increase in apoptosis rate with the synergic treatment compared to DOX alone and a 50% reduction in relative tumor volume. Finally, the TNF-\(\alpha\) and IFN-\(\gamma\) expression increased 200% and 100% compared to chemotherapeutic alone [41]. Another study employing doxorubicin is the one carried out by [PERSON] et al. (2023), which used a copolymeric nanoplatform loaded with DOX and siADP6. It obtained a reduction in tumoral cell viability and a higher apoptosis rate and inhibition rate of tumoral volume [42]. Furthermore, another study that used doxorubicin was performed by [PERSON] et al. (2020). They employed lipid nanoparticles co-carrying siRNA against UBR1, UBR2, UBR4 and UBR5 to induce the downregulation of cell migration and proliferation in liver cancer cells. With this strategy, a concentration of 0.25 nM of each siRNA resulted in a 70-80% decrease in in vitro expression of UBR1, UBR2, UBR4 and UBR5 after 72 h of exposure. In an in vivo assay, the nanoformulation induced a 75-90% reduction in the expression of these genes in the mice liver and reduced the tumor proliferation by up to 20%. In addition, the proportion of neutrophils, eosinophils and macrophages,  
\begin{table}
\begin{tabular}{c c c c c c c c} \hline
**Nanoformulation** & **Chemotherapeutic** & **siRNA** & **Target** & **Targeting Ability** & **In Vitro Results** & **In Vivo Results** & **Ref. ** \\ \hline DDAB-mPEG-PCL (nanoprecipitation method) & Regorafenib and Queretein & ASB1 & PEGylated structure (passive) & Increased cell fillers by 20\% and 55\%, respectively, compared with the free drugs. & Not performed & [38] \\  & & & & & & & \\  & & & & & & & \\  & & & & & & & \\  & & & & & & & \\  & & & & & & & \\  & & & PEGylated cytotoxicity and apoptosis induction & & was reduced by & \\  & & & & & & & \\  &  
with high Ly6C content, in the livers of the in vivo model increased between 11.5 and 13.5% compared to the untreated controls [43]. Finally, [PERSON] et al. (2020), developed pH-sensitive chitosan micelle-based nanoplatforms prepared with glycyrrhetic acid grafts on their surface loaded with siBcl2 and DOX as a tumor inhibition strategy. Furthermore, the cotreatment increased the apoptosis rate by 8.5% compared to the double administration of the siBcl2 and DOX independently. Finally, a difference in tumor volume growth of 50% was observed between combination therapy and free drug administration, with a tumor inhibition rate of 88% [44]. The chemotherapeutic agent sorafenibb was also used in the treatment of liver cancer. [PERSON] et al. (2024) employed TAT-poly-SS-lysine-modified chitosan nanoparticles to co-deliver siPD-L1 and sorafenibb. The apoptosis rate was higher in the groups treated with the complete synergistic therapy compared to the administration of the free drugs, reaching a 73% retention of the nanoplatform in the blood circulation with the synergistic therapy. Also, this combined treatment showed a better in vivo antitumor effect, with a tumor inhibition rate of 90.2 \(\pm\) 3.5% compared to the untreated controls [45]. On the other hand, [PERSON] et al. (2021) employed ultra-small lipid nanoparticles, co-loading sorafenibb and siMK.