Donor-acceptor structured photothermal COFs for enhanced starvation therapy

Targeted delivery of adequate glucose oxidase (GOX) into tumor cells by covalent organic frameworks (COFs) remains a great challenge due to their insolubility and easy aggregation. Herein, an effective strategy to synthesize nanosized donor–acceptor (D-A) structured COFs with tunable sizes, long-time water-dispersibility and special selectivity was developed. Designed D-A structure provided pathways and channels for effective charge carriers transport, and this endowed COFs with excellent photothermal property to greatly enhance starvation therapy efficiency. Large surface area and porosity in the cross-linked crystal allowed high GOX loading capacity, and further surface modification with biomolecules made it possess colloid-like water stability and targeted selectivity. All these good properties guaranteed much better in vivo and in vitro tumor ablation than single therapy, and outstanding anti-migration results were also achieved. Detailed cell apoptosis study indicated the combined therapy effectively produced reactive oxygen species, and apoptosis was induced by endogenous mitochondrial apoptosis pathway and Caspase-3 activation process, finally making cancer cells more sensitive to inadequate energy supply and high temperature. This work developed a new strategy to synthesize D-A structured photothermal COFs with good dispersibility and greatly enhance starvation therapy without any additional use of chemical drugs.