DNAzyme‐Loaded Metal–Organic Frameworks (MOFs) for Self‐Sufficient Gene Therapy

DNAzymes have been recognized as potent therapeutic agents for gene therapy, while their inefficient intracellular delivery and insufficient cofactor supply precludes their practical biological applications. Metal–organic frameworks (MOFs) have emerged as promising drug carriers without in‐depth con...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2019-05, Vol.58 (22), p.7380-7384
Main Authors: Wang, Huimin, Chen, Yuqi, Wang, Hong, Liu, Xiaoqing, Zhou, Xiang, Wang, Fuan
Format: Article
Language:English
Subjects:
Chemical compounds
Cofactors
Dismantling
DNAzymes
Drug carriers
Drug delivery
Fluorescence
Gene therapy
Metal-organic frameworks
mRNA
Nanoparticles
Payloads
Pharmacology
Photodynamic therapy
Reactive oxygen species
Zinc
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Summary:DNAzymes have been recognized as potent therapeutic agents for gene therapy, while their inefficient intracellular delivery and insufficient cofactor supply precludes their practical biological applications. Metal–organic frameworks (MOFs) have emerged as promising drug carriers without in‐depth consideration of their disassembled ingredients. Herein, we report a self‐sufficient MOF‐based chlorin e6‐modified DNAzyme (Ce6‐DNAzyme) therapeutic nanosystem for combined gene therapy and photodynamic therapy (PDT). The ZIF‐8 nanoparticles (NPs) could efficiently deliver the therapeutic DNAzyme without degradation into cancer cells. The pH‐responsive ZIF‐8 NPs disassemble with the concomitant release of the guest DNAzyme payloads and the host Zn2+ ions that serve, respectively, as messenger RNA‐targeting agent and required DNAzyme cofactors for activating gene therapy. The auxiliary photosensitizer Ce6 could produce reactive oxygen species (ROS) and provide a fluorescence signal for the imaging‐guided gene therapy/PDT. A MOF‐based DNAzyme nanosystem was reported for highly efficient combined gene silencing and photodynamic therapy (PDT). The biocompatible ZIF‐8 was utilized as a supplementary DNAzyme cofactor supplier and non‐viral vector of therapeutic DNAzymes for the activation of gene silencing while the integrated chlorin e6 (Ce6) facilitates a concomitant PDT, thus providing an intelligent self‐driven strategy for smart theranostics.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201902714