Cationic Adiposomes as a Delivery System for Neogambogic Acid for the Treatment of Multiple Cancers

Abstract

Neogambogic acid (NGA) is a potent antitumor drug but faces significant obstacles to clinical application, including extremely poor water solubility and systemic toxicity. To overcome these obstacles, a newly developed nanoparticle, adiposome, that consists of a neutral lipid core wrapped with a phospholipid-monolayer membrane, is utilized for the delivery of NGA. In this study, NGA-loaded cationic adiposomes (NGA-C-ADs) are constructed in which NGA is encapsulated within the neutral lipid core and surrounded by phospholipids and a cationic lipid. The concentration of NGA in NGA-C-ADs achieved is as high as 1.0 mg mL⁻¹, which is 2 000-fold higher than in aqueous buffer alone. Moreover, in vitro cell tests revealed that NGA-C-ADs exhibited higher cytotoxicity against various cancer cell lines compared to free NGA. In addition, in vivo anti-tumor animal studies demonstrate that NGA-C-ADs effectively inhibit tumor growth in subcutaneous CT26 tumor-bearing mice and also suppress chemically-induced hepatocellular carcinoma without obvious toxicity to major organs. These findings suggest that NGA-C-ADs hold promise as a potential treatment for multiple cancers.