Recent advances in the synthesis and shell-sheddable disassembly of acid/glutathione-degradable block copolymer nanoassemblies for drug delivery

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 the 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 under physiological conditions. Particular interest is their responses to the tumor acidic environment (pH = 4.7–6.5) and glutathione (GSH) present in the 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 the complex tumor environment. This review summarizes the recent advances in synthetic strategies for single-location ShS ABP nanoassemblies and advanced strategies for dual-location ShS/core-degradable ABP nanoassemblies, focusing on their acidic pH and GSH-responsive degradation. Furthermore, the benefits and drawbacks of these nanoassemblies in biological aspects and outlooks for effective tumor-targeting drug delivery are discussed.