Preparation of cancer cell membrane-coated Gambogic acid-loaded pH-sensitive liposomes to enhance targeted anti-hepatocellular carcinoma effect.

Abstract

Hepatocellular carcinoma has an insidious onset, and therefore, most patients are already in the middle or advanced stage once diagnosed, which seriously affects the prognosis of the patients. For a long time, it has been difficult to achieve the expected effect of the treatment that can effectively deal with the middle-or-late -stage liver cancer. Gambogic acid (GA), a dry resin secreted by the Garcinia hanbaryi Hook.f., is a natural active ingredient with various biological activities, especially the strong anti-hepatocellular carcinoma activity. However, the drawbacks such as high toxicity to the liver and kidney and low solubility have greatly limited its application. Therefore, it is necessary to develop suitable Gambogic acid formulations to overcome these disadvantages. In this study, injectable HepG2 cell membrane-modified pH-responsive liposomes (PEOz/GA@HepG2m) were prepared for active targeted delivery of Gambogic acid for the treatment of hepatocellular carcinoma. The physicochemical properties of PEOz/GA@HepG2m were evaluated in terms of the drug loading efficiency, particle size, morphology and drug release. The inhibitory effect of PEOz/GA@HepG2m on the proliferation of hepatocellular carcinoma cells was assessed by CCK8 assay and calcein-AM/PI assay in vitro. The effect of unloaded liposome PEOz@HepG2m on cellular internalization was assessed in different cell lines and it's in vivo biodistribution was analyzed by near-infrared (NIR) fluorescence imaging. The antitumor effect of PEOz/GA@HepG2m in vivo was evaluated in HepG2 tumor-bearing nude mice. The PEOz@HepG2m liposomes exhibit excellent targeting ability toward HepG2 cells. PEOz/GA@HepG2m possesses high delivery efficiency and a remarkably therapeutic effect both in vitro and vivo. The coating HepG2 cell membrane could significantly enhance the tumor-targeting effect of the liposomes and improve the antitumor effect of the loaded drug GA in vivo, indicating that the active-targeting biomimetic liposome, PEOz/GA@HepG2m, is a promising nanoplatform for delivery of drugs to hepatocellular carcinoma.