Due to the advantages of precisely spatiotemporal control and noninvasive manner, the photo-activated micelles derived from photo-responsive block copolymers have found extensive applications in controllable drug delivery systems. However, their practical utility is often constrained, due to the commercial unavailability and high difficulty in synthesis of polymerizable photosensitive monomers, tough challenge in integration of robust blood circulation ability, high toxicity of the metabolite of conventional photo-sensitive O-nitrobenzyl and azobenzene molecules. Herein, a methacryloyl-carrying, polymerizable photoacid generator (MAPDST) was synthesized and used as monomer to prepare amphiphilic photo-responsive block copolymers (PPMT) by RAFT copolymerization with acid-cleavable monomer (TTMA) in the presence of hydrophilic PEGlyated macro-RAFT agent. The structure and physicochemical characteristics of PPMT and corresponding photo-responsive micelles (PPMT NPs) were characterized. The results demonstrated that the PPMT NPs can not only have a high stability for storage and blood circulation as well as good biocompatibility, but also can quickly generate protons and thus strong acidity under UV irradiation, leading to a significant swelling and disassembly by hydrolysis of acid-cleavable TTMA segment and thus achieving a photo-switchable on–off drug release profile. This study indicated the synergistic integration of photoacid and acid-cleavable groups in polymers can provide a facile and promising strategy to endow acid-sensitive polymers and corresponding nanocarriers with desirable photo-responsiveness by photo-triggered cascade reactions. Apparently, considering the multifarious acid-sensitive groups, this new strategy can expand the substrate range of photo-responsive polymer materials and offer alternatives to develop photo-sensitive materials without the limitations associated with conventional photosensitive reagents.
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