Light-Mediated Spatiotemporally Dynamic Assembly of DNA Nanostructures in Living Cells Regulates Autophagy

The assembly of exogenous artificial architectures inside cells can regulate a series of biological events, which heavily relies on the development of spatiotemporally controlled molecular assembly systems. We herein report a designer deoxyribonucleic acid (DNA) nanostructure that enables light-mediated spatiotemporally dynamic assembly in living cells and consequently achieves efficient regulation of cell autophagy. The DNA nanostructure was constructed from i-motif moiety-containing branched DNA, photocleavable bond-containing linker, and tumor cell-targeting aptamer. After cellular uptake mediated by aptamers, under the spatiotemporal control of both UV light and late endosomal/ lysosomal acidic environments, disassembly/reassembly of DNA nanostructure occurred via two rationally designed routes, generating microsized DNA assembly. As a result, autophagy was significantly enhanced with the increase of DNA assembly size. The enhanced autophagy showed an impact on related biological effects. Our system is expected tobe a powerful tool for the regulation of intracellular events and cellular behaviors.