제목 : Simultaneous Protonation and Metalation of a Porphyrin Covalent Organic Framework Enhance Photodynamic Therapy

저널 : Journal of the American Chemical Society

링크 :  https://doi.org/10.1021/jacs.4c03519

Covalent organic frameworks (COFs) have been explored for photodynamic therapy (PDT) of cancer, but their antitumor efficacy is lim-ited by excited state quenching and low reactive oxygen species generation efficiency. Herein, we report a simultaneous protonation and metalation strategy to significantly enhance the PDT efficacy of a nanoscale two-dimensional imine-linked porphyrin-COF. The neutral and unmetalated porphyrin-COF (Ptp) and the protonated and metalated porphyrin-COF (Ptp-Fe) were synthesized via imine conden-sation between 5,10,15,20-tetrakis(4-aminophenyl)porphyrin and teraphthalaldehyde in the absence and presence of ferric chloride, re-spectively. The presence of ferric chloride generated both doubly protonated and Fe3+-coordinated porphyrin units, which redshifted and increased the Q band absorption and disrupted exciton migration to prevent excited state quenching, respectively. Under light irradia-tion, rapid energy transfer from protonated porphyrins to Fe3+-coordinated porphyrins in Ptp-Fe enabled 1O2 and hydroxyl radical gener-ation via type II and type I PDT processes. Ptp-Fe also catalyzed the conversion of hydrogen peroxide to hydroxy radical through a pho-to-enhanced Fenton-like reaction under slightly acidic condition and light illumination. As a result, Ptp-Fe-mediated PDT exhibited much higher cytotoxicity than Ptp-mediated PDT on CT26 and 4T1 cancer cells. Ptp-Fe-mediated PDT afforded potent antitumor effi-cacy in subcutaneous CT26 murine colon cancer and orthotopic 4T1 murine triple-negative breast tumors and prevented metastasis of 4T1 breast cancer to the lungs. This work underscores the role of fine-tuning the molecular structures of COFs in significantly enhancing their PDT efficacy.