A Self-Catabolic Multifunctional DNAzyme Nanosponge for Programmable Drug Delivery and Efficient Gene Silencing.

Abstract

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.

• Authors: Jing Wang, Shanshan Yu, Qiong Wu, Xue Gong, Shizhen He, Jinhua Shang, Xiaoqing Liu, Fuan Wang
• Journal: Angewandte Chemie (International ed. in English) (Angew Chem Int Ed Engl) Vol. 60 Issue 19 Pg. 10766-10774 (05 03 2021) ISSN: 1521-3773 [Electronic] Germany
• PMID: 33599385 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Wiley-VCH GmbH.

Chemical References

• DNA, Catalytic
• Nanocapsules

Topics

• DNA, Catalytic (chemistry, metabolism)
• Drug Delivery Systems
• Gene Silencing
• Genetic Therapy
• Humans
• Nanocapsules (chemistry)