Abstract:

Nanoparticle drug delivery system has played an important role in enhancing the efficacy of traditional chemotherapy drugs in recent years. However, the main challenges faced by conventional nanoparticle include poor biocompatibility, low specific targeting and slow drug release in target sites. In this work, we fabricated an efficient hepatocellular carcinoma-targeting liposome system functionalized with a redox-cleavable and homologous cell membrane(M)-targeting. The blank (P-ss-G/D@M) and drug-loaded (P-ss-G/D/Sf@M) nanoparticles coated with cell membrane were prepared by thin-film hydration method combined with electrostatic adsorption and membrane extrusion. The drug-loading amount of sorafenib was 7.2%, and the encapsulation efficiency was 79.9%. The results of in vitro drug release showed that P-ss-G/D/Sf@M accelerated drug release under reducing conditions, and the drug release rate was more than 65% at 48 hours, which was 25% higher than that under non-reducing conditions. In vitro study demonstrated that nanoparticles coated with hepatoma cell membrane were more easily taken into hepatoma cells, showing the targeting of hepatocellular carcinoma. At the same time, the disulfide bonds in the nanoparticles broke and drugs were rapidly released under the high concentration of glutathione (GSH) in the tumor cells. Compared with non-reducing sensitive drug-loaded nanoparticles, P-ss-G/D/Sf@M could significantly inhibit the growth of hepatoma cells (Hep-G2) and increase the apoptosis rate of hepatoma cells. Therefore, the homologous cell membrane-coated smart drug delivery carrier prepared herein is likely to be used to treat hepatocellular carcinoma in future.

Key words: cell membrane targeting, glutathione-response, liposomes, poly(lactic-co-glycolic acid), sorafenib