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In this study, amphiphilic block copolymer mPEG-cholic acid was synthesized in conjunction with TPGS as stabilizer to prepare multifunctional micelles. The formed polymeric micelles (PCTm) were used for the delivery of paclitaxel (PTX) and bufalin (BF). PEG group could enhance solubility and extend circulation time, while cholic acid groups achieved the liver targeted function. Combinations of these approaches could realize a synergistic therapeutic effect in the treatment of advanced hepatocellular carcinoma. CLSM  in vitro  results demonstrated that drug capsulation into PCTm could enhance cellular uptake. FCM results confirmed the uptake amount of C 6 /PCTm was 7.5-fold higher than that of free C 6  after incubation for 2 h. Competitive inhibition test proved the Na + -taurocholate co-transporting polypeptide (NTCP) involved in the uptake mechanism of PCTm. Meanwhile,  in vivo  imaging assays demonstrated that the fluorescence intensity of Cy5.5/PCTm was higher than that of free Cy5.5 on liver and tumor with extended circulation time to 48 h. In addition,  in vivo  studies confirmed that the combined therapy exhibited the strongest tumor inhibition rate of 82.29% with lower systemic toxicity. Hence, these results indicated that PCTm could provide a promising strategy for targeting hepatocellular carcinoma and achieve the goal of synergism and attenuation.

mPEG-Cholic acid/TPGS mixed micelles for combined delivery of paclitaxel and bufalin to treat hepatocellular carcinoma