Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 59, Issue 48, Pages 21648-21655Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202008413
Keywords
amplification; DNAzyme; gene silencing; microRNA; sensors
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Funding
- National Natural Science Foundation of China [21874103, 22074112]
- Fundamental Research Funds for the Central Universities [2042018kf0210, 2042019kf0206]
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The therapeutic performance of DNAzyme-involved gene silencing is significantly constrained by inefficient conditional activation and insufficient cofactor supply. Herein, a self-sufficient therapeutic nanosystem was realized through the delicate design of DNAzyme prodrugs and MnO(2)into a biocompatible nanocapsule with tumor-specific recognition/activation features. The indocyanine green (ICG)-modified DNA prodrugs are designed by splitting the DNAzyme and then reconstituted into the exquisite catalyzed hairpin assembly (CHA) amplification circuit. Based on the photothermal activation of ICG, the nanocapsule was disassembled to expose the MnO(2)ingredient which was immediately decomposed into Mn(2+)ions to supplement an indispensable DNAzyme cofactor on-demand with a concomitant O(2)generation for enhancing the auxiliary phototherapy. The endogenous microRNA catalyzes the amplified assembly of DNA prodrugs via an exquisite CHA principle, leading to the DNAzyme-mediated simultaneous silencing of two key tumor-involved mRNAs. This self-activated theranostic nanocapsule could substantially expand the toolbox for accurate diagnosis and programmable therapeutics.
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