ROS-Responsive Dimeric Prodrug-Based Nanomedicine Targeted Therapy for Gastric Cancer

Abstract

Background: Gastric cancer (GC) remains a major public health problem. Ursolic acid (UA) is reported to be effective in inhibiting GC; however, its low solubility and poor biocompatibility have greatly hindered its clinical application. Results: Herein, an innovative ROS-sensitive UA dimeric prodrug is developed by coupling two UA molecules via a ROS-cleavable linkage, which can self-assemble into stable nanoparticles in the presence of surfactant. This new UA-based delivery system comprises the following major components: Ⅰ) dimeric prodrug inner core that can achieve high drug-loading (55%, w/w) and undergo rapid and selective conversion into intact drug molecules in response to ROS; Ⅱ) a polyethylene glycol (PEG) shell to improve colloid stability and extend blood circulation, and Ⅲ) surface-modified iRGD to increase tumor targeting. Conclusion: Enhancement of the antitumor effect of this delivery system was demonstrated against GC tumors in vitro and in vivo. This novel approach offers the potential for clinical applications of UA.