Covalent organic frameworks (COFs) show great potential in biomedicine, but the synthesis of fluorescent ones with a highly conjugated structure in mild conditions remains a challenge. Herein, we reported a facile method to synthesize a nanosized, highly conjugated, and N-enriched COF material with bright fluorescence and further integrated it as a novel nanoplatform for efficient cancer starvation/gas therapy. High surface area and a porous structure endowed COFs with large loading capacity for both glucose oxidase and l-arginine, while conjugated monomer and N-doping guaranteed bright fluorescence and relatively strong interactions between loaded cargos. Well-designed size allowed easy cell uptake of drug-loaded COFs, which finally resulted in a highly efficient starvation therapy by consuming large amounts of glucose in cancer cells. H2O2, the byproduct during glucose consumption, was made full use of oxidizing l-arginine to generate toxic NO. This constructed combined starvation and gas therapy and exhibited emerging antimigration performance. Both in vitro and in vivo experiments confirmed an excellent cancer therapeutic effect than a single therapy, and the novel therapeutic platform showed good biocompatibility. Detailed mechanism study demonstrated that cell apoptosis and lysosomal damage contributed most to the synergistic treatment. Our study developed a new strategy to synthesize highly conjugated COFs with fluorescence and reported the potential applications in cancer therapy.
Keywords: COFs; drug delivery; nanomaterials; structure design; synergistic therapy.