Gene

Quantum mechanics

Genetic enhancement

Photosensitizer

Biology

Photodynamic therapy

Photochemistry

Materials science

Cancer research

Biochemistry

Deoxyribozyme

Combinatorial chemistry

Physics

Nanotechnology

Organic chemistry

Fluorescence

Medicine

Chemistry

Biophysics

BODIPY

Angewandte Chemie International Edition

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.

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