Glycyrrhetinic acid-decorated and docetaxel-loaded thermosensitive liposomes for combination therapy against hepatocellular carcinoma

This report focused on a novel nano-drug delivery system (GA-DTX-PVP/CuS-TSL) by combining glycyrrhetinic acid, copper sulfide nanoparticles, and docetaxel (DTX) with thermo-sensitive liposomes, which not only could achieve drug targeting distribution, but also could combine chemotherapy with phototherapy for tumor therapy. The particle size and DL of GA-DTX-PVP/CuS-TSL were 251.2 ± 0.40 nm (PDI = 0.15) and 7.51 ± 0.15%, respectively. The physicochemical properties, pharmacokinetics, biodistribution, and antitumor effects in vitro and in vivo of GA-DTX-PVP/CuS-TSL were also carried out. The result showed GA-DTX-PVP/CuS-TSL had obvious slower and temperature-dependent drug release effect when compared with DTX solution and DTX-PVP/CuS-TSL. In comparison to DTX solution group, the cell growth inhibition rates of DTX-PVP/CuS-TSL and GA-DTX-PVP/CuS-TSL groups on SMMC-7721 cells were significantly enhanced under the same conditions. Furthermore, when combined with 808 nm laser irradiation, the cell growth inhibition rates of DTX-PVP/CuS-TSL and GA-DTX-PVP/CuS-TSL groups were further enhanced. Moreover, GA-DTX-PVP /CuS-TSL could prolong the circulation time of DTX in vivo and improve the targeted distribution of DTX at the tumor sites of S 180 tumor-bearing mice. When combined with 808 nm of near-infrared light irradiation, GA-DTX-PVP/CuS-TSL had much more obvious anti-tumor activity both in vitro and in vivo than that of DTX solution and DTX-PVP/CuS-TSL. This study may provide certain theoretical basis for safe and effective treatment of tumor.