Glucose oxidase-mediated non-covalent functionalization unlocks long-term monodispersity of donor-acceptor COFs for synergistic cancer therapy.

Covalent organic frameworks (COFs) hold immense promise for widespread applications, yet their inherent insolubility and irreversible aggregation in aqueous media remain a long-standing fundamental barrier that severely limits their translational potential. Herein, we report a rapid, non-covalent enzymatic functionalization strategy that leverages glucose oxidase to confer robust, long-term monodispersity to donor-acceptor (D-A) COFs under physiological conditions. The unique D-A electronic structure of the COFs not only provides abundant anchoring sites for uniform gold nanoparticle immobilization but also facilitates efficient photogenerated charge separation, resulting in a record-high photothermal conversion efficiency. The resulting nanoplatform exhibits exceptional synergistic therapeutic efficacy: it generates abundant reactive oxygen species upon near-infrared irradiation, triggers robust apoptosis via the endogenous mitochondrial pathway, and demonstrates remarkable inhibition of tumor cell migration. This work establishes a generalizable green strategy to fundamentally address the intractable aggregation problem of COFs in aqueous solutions, and provides a non-invasive, chemotherapy-free therapeutic platform that achieves superior anticancer activity at ultra-low doses.