Recent advances in development of imine-based acid-degradable polymeric nanoassemblies for intracellular drug delivery

Abstract

Acid-responsive degradable nanoassemblies self-assembled from amphiphilic block copolymers with acid-labile linkages have been extensively explored as effective intracellular drug delivery vehicles for chemotherapy. They degrade in tumoral and endo/lysosomal acidic environments (pH = 4.0–6.9), leading to enhanced/controlled release of encapsulated or conjugated drug molecules. In particular, imine (C=N) and its family of benzoic imine, hydrazone, and oxime are promising acid-labile linkages owning to their facile synthesis and tunable acid-responsive degradation. This review summarizes the recent advances in the design and synthesis of imine-bearing block copolymers and their nanoassemblies in three typical forms as self-assembled nanoassemblies, core-crosslinked nanogels, and polymer-drug conjugates. Numerous synthetic strategies to synthesize effective nanoassemblies with different numbers and locations of imine linkages are focused to elucidate their disassembly mechanism and enhanced drug release in acidic tumor environments.