AIEgen-Based sp²Carbon-Conjugated Covalent Organic Frameworks with High Stability and Emission for Activatable Imaging and Ferroptosis in Target Tumor Cells

Synthesis of highly stable and emissive covalent organic frameworks (COFs) for biological applications is urgently needed. Herein, we developed a novel AIEgen-based sp²carbon-conjugated COF (sp²c-COF) for activatable imaging and ferroptosis in target tumor cells. The sp²c-COF_TFBE-PDANwas obtained by employing tetra-(4-aldehyde-(1,1-biphenyl)) ethylene (TFBE) as an AIEgen unit and 1,4-phenylenediacetonitrile (PDAN) as a linker through the Knoevenagel reaction. The as-obtained COF_TFBE-PDANexhibited high chemical stability even in 3 M HCl and 3 M NaOH and 146-fold quantum yield enhancement compared with the corresponding imine-linked COF due to the C═C linkages and the AIEgens. The luminescence of COF_TFBE-PDANwas dramatically quenched by a tannic acid (TA)-based metal phenolic network (Fe^IIITA), which was formed via Fe(III)-directed metal-polyphenol coordination. After modified with polyethylenimine (PEI), COF_TFBE-PDAN@Fe^IIITA-PEI was used for activatable imaging and ferroptosis. Fe^IIITA was dissociated in overexpressed glutathione (GSH) and the acidic lysosomal environment, which resulted in the recovery of luminescence and in situ Fe²⁺production. Overloaded H₂O₂in tumor cells could further react with Fe²⁺to produce reactive oxygen species (ROS) via the Fenton reaction. GSH depletion and ROS production led to lipid peroxide accumulation-mediated ferroptosis. The luminescence recovery of COF_TFBE-PDANalso enabled it to act as a self-reporter for the decomposition of Fe^IIITA and imaging in tumor cells. This study shows that AIEgen-based sp²c-COF displays great potential for tumor cell imaging and therapy.