A Bimetallic Metal–Organic Framework Encapsulated with DNAzyme for Intracellular Drug Synthesis and Self‐Sufficient Gene Therapy

Abstract Although chemotherapy is one of the most widely used cancer treatments, there are serious side effects, drug resistance, and secondary metastasis. To address these problems, herein we designed a bimetallic metal–organic framework (MOF) encapsulated with DNAzyme for co‐triggered in situ cancer drug synthesis and DNAzyme‐based gene therapy. Once in cancer cells, MOFs would disassemble and liberate copper ions, zinc ions, and DNAzyme under the acidic environment of lysosomes. Copper ions can catalyze the synthesis of the chemotherapeutic drug through copper‐catalyzed azide–alkyne cycloaddition (CuAAC) reaction after being reduced to Cu I ; zinc ions act as the cofactor to activate the cleavage activity of DNAzyme. The anticancer drug is synthesized intracellularly and can kill cancer cells on site to minimize side effects to normal organisms. The activated DNAzyme starts gene therapy to inhibit tumor proliferation and metastasis by targeting and cleaving oncogene substrates.