Fabrication of hyaluronic acid-based micelles with glutathione-responsiveness for targeted anticancer drug delivery

Abstract

Hyaluronic acid (HA), a natural polymer, has gained much attention recently because of its good biocompatibility and extensive availability. Herein, a novel drug delivery system based on hyaluronic acid-tetraphenyl ethylene conjugate (HA-SS-TPE) with glutathione (GSH)-responsiveness for targeted drug delivery is designed. During the self-assembly of HA-SS-TPE, doxorubicin (DOX) is loaded to form DOX-loaded polymeric micelles. These as-prepared DOX-loaded polymeric micelles not only exhibit fluorescent emission, but also fast glutathione-triggered dissociation to unload DOX by responding to tumor microenvironments. In-vitro investigations showed that the DOX-loaded polymeric micelles presented a higher intracellular release ratio in CD44-positive cells (ES2 and Hela) than in CD44-negative cells (MCF-7 and L929). Notably, in vivo investigations showed that DOX@HA-SS-TPE significantly suppressed tumor growth. As a result, such a GSH-responsive drug delivery system with fluorescent feature provides a potential treatment for CD44-overexpressing cancers.