Mitochondria-Targeting-Based of Paclitaxel-Loaded Triphenylphosphine-Pluronic F127-Hyaluronic Acid Nanomicelles in Multi-Drug Resistant Hepatocellular Carcinoma

Abstract

Background: In this study a new novel nanomicelle (TPH) sco-loaded with triphenylphosphine (TPP)-Pluronic F127-hyaluronic acid (HA) and Paclitaxel (PTX) has been designed to treat multidrug resistant hepatocellular carcinoma (HCC). Methods: TPH was initially synthesized by ester bond formation with mitochondria-targeting TPP agent and TPH nanomicelles loaded with PTX (TPH/PTX) had outstanding physical characteristics in human multi drug-resistant HCC cell line Bel7402/5-FU. Cytotoxicity and hemocompatibility assessments, nanomicelle cellular absorption and mitochondrial targeting, and in vivo xenograft imaging was used to evaluate that the nonemicells delivered into target cell and components. Results: The results of fluorescence test showed that TPP could promote the fusion of nanomicells to human multi drugresistant HCC cell line Bel7402/5-FU, and targeted the mitochondria, and also improved the targeting and retention of drugs in liver tumors. The results of cell efficacy showed that TPH/PTX induced a strong apoptosis effect, which could significantly reduce the mitochondrial membrane Zeta potential, increase the level of intracellular ROS and the release of Caspase-3, significantly enhanced the pro-apoptotic protein (Bcl-2), decrease the expression level of anti-apoptotic protein (Bax). Conclusion: TPH/PTX has a promising mitochondrial targeting function, and can enhance the effect of drugs on promoting apoptosis of drug resistant HCC cells.