Biotin-Targeted Multifunctional Nanoparticles Encapsulating 10-Hydroxycamptothecin and Apoptin Plasmid for Synergistic Hepatocellular Carcinoma Treatment

Hepatocellular carcinoma (HCC) is a common cause of death, and there is a lack of effective treatment methods along with observed drug resistance. As compared to traditional treatments, drug delivery systems have been extensively studied and come with unique advantages, but their clinical applications are limited due to their poor therapeutic efficacy and severe cytotoxicity. However, multifunctional nanoparticles (MNPs) provide a strategy for the clinical treatment of tumors. In this study, MNPs were constructed with a poly(lactic-co-glycolic acid)-ε-polylysine (PLGA-EPL) vehicle for the codelivery of 10-hydroxycamptothecin (HCPT) and apoptin plasmid (AP) to synergistically treat HCC. MNPs were surface-modified with biotin (BIO) to improve their ability to target liver tumor cells. Blank MNPs showed good biocompatibility in cytotoxicity assays and acute toxicity tests in BALB/c mice. These MNPs also displayed a good targeting ability as evidenced by flow cytometry and confocal scanning laser microscopy analyses. The controlled release ability of these MNPs was confirmed by drug release and blank nanoparticle degradation assays in vitro. In vivo antitumor experiments demonstrated the synergistic anticancer effects of the MNPs, while the synergistic anticancer mechanism was further explored by Western blotting. Moreover, this study greatly increased the loading capacity of AP, suggesting the exceptional potential of MNPs for the treatment of HCC.