Multifunctional nanoparticles for targeted delivery of apoptin plasmid in cancer treatment

Abstract

Abstract The systemic toxicity and low efficacy of traditional chemotherapy for hepatocellular carcinoma (HCC) result in poor clinical outcomes. This study was designed to achieve targeted delivery of apoptin plasmid (AP) to liver tumors and killing of cancer cells using multifunctional nanoparticles (MFNPs) having sustained-release properties. The MFNPs featuring a distinct core-shell structure were prepared using poly(lactic-glycolic acid)-ε-polylysine copolymer and loaded with AP by adsorption. Specific targeting of liver tumor cells was achieved by biotinylation of the nanoparticles (NPs), while an improvement in lysosomal escape and nuclear localization enhanced the tumor cell killing capability of AP. Blank MFNPs exhibited good biocompatibility while AP-loaded NPs were found to exert strong inhibitory effects on both tumor cells in vitro and solid tumors in vivo. Taken together, these findings demonstrate a promising route for the development of tumor-targeted NPs which may lead to improved therapeutic strategies for treating HCC.