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

Abstract

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.

Keywords: DNAzymes; drug delivery; gene therapy; metal-organic frameworks; photodynamic therapy.