A self-catabolic smart DNAzyme nanocapsule for amplified chemo-photodynamic therapy†

Violent degradation strategies of traditional nucleic acid hydrogels may bring adverse toxicity to complex biological systems when administered systemically due to uncontrolled digestion. Herein, an Mn²⁺-driven self-catabolic smart deoxyribozyme (DNAzyme) nanocapsule is developed for precise on-demand drug release to amplify cancer chemo-photodynamic therapy. Loaded manganese dioxide (MnO₂) can generate oxygen (O₂) to overcome tumor hypoxia and enhance photodynamic therapy, and a microRNA-21 (miR-21) antisense sequence can adsorb and clear intracellular miR-21 to amplify chemotherapy. The encoded DNAzymes and substrate sequences enable the programmable digestion of nucleic acid hydrogel carriers with Mn²⁺ ions as cofactors, so as to accurately deliver various therapeutic drugs. The results show that the smart nanocapsules can amplify chemo-photodynamic therapy by improving hypoxia in the tumor microenvironment and functional genes to kill tumor cells, which is expected to play an important role in tumor diagnosis and treatment.