Near-Infrared Light Laser-Triggered Release of Doxorubicin and Sorafenib from TemperatureSensitive Liposomes for Synergistic Therapy of Hepatocellular Carcinoma

Abstract

Chemotherapy of hepatocellular carcinoma (HCC) is facing drug resistance, which leads to unsatisfactory therapeutic effect. Thus, a combination therapy using multiple drugs may overcome this challenge. The current study aims to realize a synergistic chemotherapy of HCC by using a near-infrared light (NIR) responsive nanocarrier to co-deliver the chemotherapeutic drug Doxorubicin (DOX) and molecular targeting agent Sorafenib (SF). The nanocarrier, which could effectively load DOX in its aqueous core while SF and IR-780 in its lipid bilayer, is fabricated from a temperature-sensitive liposome (TSL) modified with PF127. An efficient SF and DOX co-loading was achieved, and meanwhile the effective photothermal conversion of IR-780 under NIR laser may cause a disassembly of the liposome structure which may trigger a rapid drug release in tumor site, greatly boosting the synergetic chemotherapeutic effect. The NIR laser-triggered drug release and the synergistic anti-tumor effect were evaluated both in cell and animal experiments, which revealed that the PF127-modified TSL is a potent nanoplatform to improve the HCC treatment through co-delivering a drug combination.