Photoactivated Self‐Disassembly of Multifunctional DNA Nanoflower Enables Amplified Autophagy Suppression for Low‐Dose Photodynamic Therapy

Low-dose photodynamic therapy (PDT) holds great promise for reducing undesired patient photosensitivity in cancer treatment. Yet, its therapeutic effect is significantly affected by intracellular cytoprotective processes, such as autophagy. Here, an efficient autophagy suppressor is developed, which is a multifunctional DNA nanoflower (DNF) consisted of tumor-targeting aptamers and DNAzymes for silencing autophagy-related genes, with surface modification of low-dose photosensitizer (Ce6). It is found that the multifunctional DNF can specifically target tumor cells and generate reactive oxygen species (ROS) under light irradiation to trigger self-disassembly of DNF, enhancing the bioavailability of encoded DNAzymes, leading to amplified autophagy suppression. As a facile spatiotemporally programmable photogene therapy platform, the designed DNF is able to suppress tumor growth in vivo with a very low injection dose of Ce6 (18 µg kg-1 , around 100 times lower than the generally applied dose), representing a promising strategy for cancer therapy with safely low-dose PDT.