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A Smart Theranostic Nanocapsule for Spatiotemporally Programmable Photo‐Gene Therapy
Author(s) -
Gong Xue,
Li Ruomeng,
Wang Jing,
Wei Jie,
Ma Kang,
Liu Xiaoqing,
Wang Fuan
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202008413
Subject(s) - deoxyribozyme , chemistry , prodrug , nanotechnology , gene silencing , photothermal therapy , biophysics , dna , biochemistry , gene , materials science , biology
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.