PLGA nanoparticles containing α-fetoprotein siRNA induce apoptosis and enhance the cytotoxic effects of doxorubicin in human liver cancer cell line

Hepatocellular carcinoma (HCC) is one of the most common cancers and is a leading cause of death. Delivery of therapeutic molecules, e.g., siRNA, to HCC cells could potentially be an alternative treatment for HCC. In this study, the siRNA targeting α-fetoprotein (AFP) mRNA was found to specifically induce apoptosis and significant cell death in HepG2 cells. It also enhanced the cytotoxic effects of doxorubicin by about two-fold, making it the candidate therapeutic molecule for HCC treatment. To deliver the siRNAs into HCC cells, the AFP siRNAs were loaded into the nanoparticles based on poly (lactic-co-glycolic) acid (PLGA). These nanoparticles induced apoptosis in HepG2 cells and synergistically increased the cytotoxicity of doxorubicin. In summary, the delivery of the AFP siRNA-loaded PLGA nanoparticles in combination with doxorubicin could be a very promising approach for the treatment of HCC. •Alpha-fetoprotein (AFP) plays an important role in the development and progression of hepatocellular carcinoma (HCC).•The AFP siRNA-containing PLGA nanoparticles (NP) cause specific and significant cytotoxicity via apoptosis in HepG2 cells.•The PLGA NPs can also significantly enhance the cytotoxicity of doxorubicin.•Combined treatment using the PLGA NPs and doxorubicin could be an alternative therapy for HCC.