Nanoparticle delivery and combination therapy of gambogic acid and all-trans retinoic acid

Abstract

Jing Yao, Yuanke Li, Xiaojing Sun, Fatima Zohra Dahmani, Hongpan Liu, Jianping Zhou State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: In order to enhance the in vivo codelivery efficiency of gambogic acid (GA) and all-trans retinoic acid (ATRA), our strategy was to entrap GA in the self-assembled nanoparticles based on amphiphilic hyaluronic acid (HA)-ATRA (HRA) conjugate. In this way, GA and ATRA were loaded simultaneously in a nanocarrier and codelivered into the tumor cell through HA receptor-mediated endocytosis. GA-loaded HRA nanoparticles (GA-HRA) were prepared by a dialysis method, and their physicochemical characteristics were investigated as well. GA-HRA exhibited a high drug loading capacity (31.1%), had a particle size in the range of 100–150 nm, and good biocompatibility. HRA nanoparticles were effectively internalized by MCF-7 cells and translocated into the nucleus in a time-dependent manner. The in vivo imaging analysis demonstrated that the fluorescent signals in the tumor were markedly increased with DiR-loaded nanoparticles after intravenous administration compared to free DiR solution, suggesting it has excellent tumor targeting properties. More importantly, GA-HRA exhibited excellent in vivo efficacy with dramatically reduced toxicity. In conclusion, with the assistance of HRA nanoparticles, GA and ATRA can successfully realize an effective combination chemotherapy as well as tumor-targeted delivery. Keywords: tumor targeting, nanoparticles, hyaluronic acid