Assembly simulation and synergistic chemotherapy of TPGS derivative functionalized polymersomes in hepatocellular carcinoma

Aim: Multidrug resistance and severe side effects lead to poor therapeutic efficacy of monotherapy against hepatocellular carcinoma. Here, a targeting codelivery nanocomposite system is constructed to reverse tumor multidrug resistance and realize a combination therapy of doxorubicin and oxaliplatin. Methods & materials: We simulate the composited structure of TPGS-lactobionic acid conjugate (TLA) modified methyl poly(ethylene glycol)-polylactide (mPP) polymersomes using dissipative particle dynamics. Cellular uptake and drug retention, cytotoxicity, in vivo antitumor efficacy and toxicity were evaluated. Results: TLA/mPP composited polymersomes improved intracellular accumulation of coloaded drugs via active targeting ability and P-gp efflux inhibition, leading to strong cytotoxicity against HepG2/ADR cells and potent tumor inhibition (93.5%) for HepG2/ADR tumor. Conclusion: TLA/mPP composited polymersomes represent a promising multifunctional nanoplatform against hepatocellular carcinoma.Graphical abstract