Nanosized\nPorphyrin-Containing Covalent Organic Polymer\nto Enhance Ferroptosis in Photodynamic Treatment of Tumor Cells via\nGlutathione Depletion

A porphyrin-containing\nnanoscale covalent organic polymer\n(COP)\nwas fabricated from 5,10,15,20-tetra(4-carboxyphenyl)porphyrin (TCPP)\nand cystamine via an acylation reaction. On the one hand, TCPP can\ninduce tumor cell death by laser irradiation. Due to the presence\nof disulfide bonds of cystamine which can react with glutathione,\nit exhibits depletion of glutathione and accumulation of peroxides\nin tumor cells. Ultimately by the hyaluronic acid to encapsulate the\nCOP to get S-COP@HA, the nanoparticle with a size of 168.6 nm also\nexhibits good tumor accumulation and biosafety. Significant inhibition\nof tumor cell growth was observed after two consecutive doses of S-COP@HA\nat relatively low laser densities. This combination therapy was proved\nto reduce the level of reduced glutathione in tumor cells, where ferroptosis\noccurs after photodynamic treatment. Overall, this study presents\na potent, good therapeutic option for the effective enhancement of\nphotodynamic therapy by glutathione depletion.