Porous organic polymer overcomes the post-treatment phototoxicity of photodynamic agents and maintains their antitumor efficiency

• Published in: Acta biomaterialia Vol. 150; pp. 254 - 264
• Main Authors: Liu, Yamin, Wang, Ze-Kun, Gao, Zhong-Zheng, Zong, Yang, Sun, Jian-Da, Zhou, Wei, Wang, Hui, Ma, Da, Li, Zhan-Ting, Zhang, Dan-Wei
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 15.09.2022
• Subjects: Photodynamic therapy; Phototoxicity reduction; Porous organic polymer; Porphyrin photosensitizer; Safety improvement; Porous organic polymer; Porphyrin photosensitizer; Photodynamic therapy; Safety improvement; Phototoxicity reduction
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2022.07.043

Since 1995, photodynamic therapy (PDT) has been utilized as an effective method for cancer treatment. However, the residues of photosensitizers in the normal tissues after PDT can be activated by sunlight to cause severe skin phototoxicity, for which currently there are no clinical solutions. As a result, post-PDT patients need to remain out of sunlight for up to five weeks, which produces great living and mental burdens for patients. Herein, we report that a biocompatible porous organic polymer (POP) with average 3.1 nm porosity is able to suppress the skin phototoxicity of clinically used porphyrin-based photodynamic agents (PDAs), including Photofrin, Talaporfin and Hiporfin, through an adsorption-elimination mechanism. Fluorescence titration and dialysis experiments show that POP can adsorb and retain the PDAs at a micromolar concentration. In vivo experiments demonstrate that POP can significantly suppress the skin phototoxicity caused by all the three PDAs without reducing their PDT efficacy. Up to now, no efficient clinical treatment for the inhibition of post-PDT phototoxicity of clinically used porphyrin-based PDAs is available. In the manuscript, a water-soluble cationic porous organic polymer has been revealed to include three clinically used PDAs. In vivo experiments show that this inclusion remarkably reduces the content of PDAs in mouse skins, leading to significant alleviation of their post-PDT phototoxicity without no negative effect on their PDT efficacy. Thus, this work provides a strategy for overcoming the drawback of clinically used photodynamic agents. [Display omitted]