## 3 Results
### Nanoparticles for Pancreatic Cancer Treatment  
Different strategies for the treatment of pancreatic cancer have been employed among the studies analyzed in this systematic review, using different combinations of chemotherapeutics, and siRNAs targeting different aspects of the neoplasm have been encapsulated in nanoparticles. Inside these, a great proportion of studies included chemotherapeutic gemcitabine as a co-therapy with siRNA. In this context, [PERSON] et al. (2020) employed polymeric trilamellar micelles, co-loaded simultaneously with NF-kB. This treatment induced a significant increase in apoptosis and inhibition of cell migration compared with chemotherapy alone [55]. Furthermore, another study, carried out by [PERSON] et al. (2019), employed cationic liposomes co-loaded simultaneously with gemcitabine and siMcl-1. The combined treatment induced a 40% and 27% increase in cell cytotoxicity compared with the siRNA and gemcitabine treatments alone, respectively. In addition, the tumor volume decreased by 83.33% with the complete LP-Gem-siMcl therapy reaching a minimum size compared to the chemotherapeutic alone and 90% with the PBS control [56]. [PERSON] et al. (2021) used a core-shell micelle-like nanocomplex based on a conjugation of cholesterol to the N-termination of short peptides and a labile dipeptide of cathepsin B (Val-Cit) to load siPCBP2 combined with gemcitabine. This was to try to reverse the accumulation of type I collagen in the tumor stroma and induce antitumor activity. It achieved a 97% reduction in PCBP2 mRNA expression with synergic treatment and decreased \(\alpha\)CP2 and type I collagen levels by 82% and 70%, respectively, with respect to the siRNA alone. Moreover, the combination of gemcitabine and the siRNA nanocomplex induced the highest inhibition of collagen expression in the tumor in vivo with 46.8%. Also, the combined synergic therapy reduced tumoral volume by 36.66% compared to gemcitabine alone [57]. Another study employed gemcitabine co-administered independently with the gene silencing using a dextran-coated ferric magnetic nanocarrier that delivers siPD-L1 as  
\begin{table}
\begin{tabular}{c c c c c c c c} \hline
**Nanoformulation** & **Chemotherapeutic** & **siRNA** & **Targeting Ability** & **In Vitro Results** & **In Vivo Results** & **Ref. ** \\ \hline ZnAsOx in a matrix of SiO2 (“one-pot” reverse emulsification) & Arsenic trioxide & SHP-1 & NS & A 39\% reduction in cell viability and & A 2.2-fold and metastasis in the 20\% increase in apoptosis rate with the synergic treatment compared to chemotherapeutic alone. & A 2.2-fold and metastasis 3.5-fold reduction in tumor growth and metastasis in the 20\% increase in apoptosis rate with the synergic treatment compared to chemotherapeutic alone. & A 2.2-fold and metastasis 3.5-fold reduction in tumor growth and metastasis in the 20\% increase in apoptosis rate with the synergic treatment compared to chemotherapeutic alone. & A 6.66\% tumoral volume reduction with the synergic treatment compared to the one without the drug. & A 6.  
an anti-tumor strategy. This strategy showed a higher tumor volume decrease, with a 93.75% reduction between the synergic high-dose treatment and gemcitabine alone. The combined treatment increased the recruitment of CD8\({}^{+}\) tumor-infiltrating lymphocytes (TILs) with increased cell-mediated cytotoxicity, indicating an initiation of antitumor immune response [58]. The last study that employed gemcitabine was performed by [PERSON] et al. (2021). They used nanoparticles with a polymeric antagonist of CXCR4 (overexpressed in pancreatic cancer) and cholesterol to deliver siRNA1 to enhance the effect of gemcitabine. This therapy achieved a synergistic effect, achieving a 30% reduction in cell viability compared with free gemcitabine. In a xenograft tumor model, this combined therapy obtained the greatest tumor weight reduction, with a 3.75-fold reduction between synergic treatment and the gemcitabine alone [59]. Other studies applied paclitaxel as the main chemotherapy.