A highly atom-economical bioactive nanocarrier for synergistically enhanced antitumor with reduced liver injury

Abstract

The development and application of nano-drug carrier systems have opened up unprecedented opportunities for tumor treatment. However, eliminating the related liver toxicity is still very challenging because hepatotoxicity is the most severe adverse effect of chemotherapy and nanotherapy. Herein, a highly atom-economical bioactive nanocarrier delivery system is shown. This carrier is assembled from oleanolic acid (OA), which is abundantly present in Chinese medicinal plants and has shown potent antioxidant, antitumor, and hepatoprotective properties. Molecular simulation and experimental characterization have demonstrated that the assembly process of OA-encapsulated paclitaxel (PTX) to form OA–PTX nanoparticles is mainly through hydrophobic interactions and hydrogen bonding interactions. In vitro and in vivo experiments confirmed that OA and PTX have synergistic antitumor effects due to their different antitumor mechanisms. As expected, liver injury induced by PTX was significantly reduced due to the hepatoprotective activity of OA. The prepared nanomedicine has high drug loading capacity and excellent targeting, as well as good biocompatibility and low in vivo toxicity, which ensure the effectiveness of the tumor treatment and the safety of the body. The present study provides new ideas for the development of nanocarriers and avenues for active natural products in reducing drug side effects.