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 C6/PCTm was 7.5-fold higher than that of free C6 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.