Recent Advances in Synthesis and Shell-Sheddable Disassembly of Acid/Glutathione-Degradable Block Copolymer Nanoassemblies for Drug Delivery

Abstract

Shell-Sheddable (ShS) nanoassemblies based on well-defined amphiphilic block copolymers (ABPs) exhibiting stimuli-responsive degradation (SRD) have been extensively investigated for the detachment of poly(ethylene glycol) corona as tumor-targeting drug delivery systems. They are designed to respond to triggers found in the cellular environment, while being stable in physiological conditions. Particular interests are responses to tumor’s acidic environments (pH = 4.7–6.5) as well as glutathione (GSH) present in cytosol of tumor tissues. Moreover, dual location ShS nanoassemblies have been explored with endogenous acidic pH and GSH stimuli to achieve enhanced/accelerated, systematic drug release profiles in tumor’s complex environments. This review summarizes recent advances on synthetic strategies for single location ShS ABP nanoassemblies and advanced strategies for dual location ShS/core-degradable ABP nanoassemblies with focus on acidic pH and GSH-responsive degradation. This review further describes the benefits and drawbacks of these nanoassemblies on biological aspects and outlooks for effective tumor-targeting drug delivery.