MitoSiege-Driven Catalase Collapse: A GSH-Responsive, Mitochondria-Targeted COF Prodrug for Amplified Chemodynamic Therapy.

ABSTRACT: Chemodynamic therapy (CDT), leveraging Fenton reactions to generate hydroxyl radicals (•OH) from intracellular hydrogen peroxide (H₂O₂), offers a promising cancer treatment strategy due to its high specificity and low systemic toxicity. However, the targeted delivery of •OH-producing prodrugs using covalent organic frameworks (COFs) remains a significant challenge. Here, we report a mitochondria-targeted COF-based nano prodrug, COF-31@P, designed for enhanced CDT efficacy. COF-31@P is composed of a Fenton-like copper complex and the hydrogen peroxide enzyme inhibitor 3-amino-1,2,4-triazole (3-AT), linked via disulfide bonds that are selectively cleaved by tumor-specific glutathione (GSH). This cleavage triggers the release of active components, resulting in robust •OH

SUBMITTER: Ding Q 

PROVIDER: S-EPMC12559460 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature