Preparation and evaluation of folate-decorated human serum albumin nanoparticles for the targeted delivery of sorafenib to enhance antihepatocarcinoma efficacy

Sorafenib is a multitarget tyrosine kinase inhibitor for the first-line treatment of hepatocellular carcinoma (HCC). However, moderate therapeutic effects are common in the clinic. Nanotechnology has provided feasible strategies to solve this problem. In the current study, we coated sorafenib with human serum albumin (HSA) and grafted folic acid (FA) onto the nanoparticle surface (FA-HSA-SRF-NPs) to enhance tumor targeting. Our results showed that the new nanoparticles had a high loading efficiency with a small diameter and good stability. In vitro, the FA-HSA-SRF-NPs showed enhanced cytotoxicity against hepatocellular BEL-7402 cells and increased the safety for normal liver LO2 cells. In vivo, FA-HSA-SRF-NPs exhibited effective antitumor activity toward nude mice bearing xenograft tumors without systemic toxicity, and this antitumor activity manifested as the inhibition of tumor proliferation and suppression of tumor angiogenesis. In addition, FA-HSA-SRF-NPs notably enhanced the accumulation of sorafenib in the tumor tissues of mice and markedly increased the amount of sorafenib in systemic circulation in rats. This current study indicated that FA-HSA-SRF-NPs could increase the efficacy of sorafenib against liver tumors that highly express the folate receptor (FR) and possess good safety, thereby highlighting their potential clinical value.