Development and disassembly of single and multiple acid-cleavable block copolymer nanoassemblies for drug delivery

Drug delivery via block copolymer nanoassemblies has been widely viewed as an efficient way to augment therapeutic efficiency of anticancer drugs for cancer therapy. Acid-degradable block copolymer-based nanoassemblies are promising intracellular candidates for tumor-targeting drug delivery as they exhibit enhanced release of encapsulated drugs through their dissociation (or disintegration) upon cleavage of acid-labile linkages in response to a tumor's acidic environment (pH = 4.2-6.7). Furthermore, degradation of the self-assemblies via acid-catalyzed hydrolysis can be tuned with a choice of various available acid-labile linkages. This review summarizes recent advances in the synthesis and disassembly of acid-cleavable block copolymers for controlled drug delivery. Strategies to integrate acid-labile covalent linkages in block copolymers at different locations, as in micelle cores and core/corona interfaces are particularly focused upon. Additionally, elegant strategies that allow for the synthesis of dual acid/reduction, acid/light, acid/enzyme-degradable block copolymer systems with cleavable linkages in single or dual locations are discussed.