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A Self‐Catabolic Multifunctional DNAzyme Nanosponge for Programmable Drug Delivery and Efficient Gene Silencing
Author(s) -
Wang Jing,
Yu Shanshan,
Wu Qiong,
Gong Xue,
He Shizhen,
Shang Jinhua,
Liu Xiaoqing,
Wang Fuan
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202101474
Subject(s) - deoxyribozyme , nanotechnology , gene silencing , chemistry , drug delivery , gene delivery , aptamer , ribozyme , computational biology , dna , microbiology and biotechnology , gene , genetic enhancement , biology , biochemistry , materials science , rna
DNAzyme‐based gene therapy holds immense prospects for effectively treating severe diseases, yet is constrained with inefficient delivery and unconditional activation. Herein, we designed a bioinspired self‐catabolic DNA nanocapsule for sustaining tumor‐specific cascade activation of therapeutic DNAzyme. The exquisite DNAzyme was temporarily masked by the self‐excising DNAzyme in the hierarchical rolling circle replication (RCR) nanostructures, thus stayed in an inactive state in physiological fluids. Through the multivalent tumor‐anchoring aptamer strands, the RCR nanocapsule was specifically accumulated in cancer cells and was sequentially activated for motivating the ultimate DNAzyme‐mediated gene silencing via the intelligent stimuli‐responsive cascade DNAzyme activation. By virtue of the programmable RCR assembly strategy, our compact DNAzyme nanoplatform shows great promise for developing versatile smart gene therapeutics and personalized nanomedicines.