An unexpected strategy to alleviate hypoxia limitation of photodynamic therapy by biotinylation of photosensitizers

• Published in: Nature communications Vol. 13; no. 1; pp. 2225 - 10
• Main Authors: An, Jing, Tang, Shanliang, Hong, Gaobo, Chen, Wenlong, Chen, Miaomiao, Song, Jitao, Li, Zhiliang, Peng, Xiaojun, Song, Fengling, Zheng, Wen-Heng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.04.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 14/34; 639/638/298/54/152; 639/638/309/2420; 639/638/439/943; Anions; Biotin; Biotinylation; Design; Fluorescein; Humanities and Social Sciences; Humans; Hypoxia; Hypoxia - drug therapy; Irradiation; Light irradiation; multidisciplinary; Oxygen; Oxygen consumption; Photochemotherapy - methods; Photodynamic therapy; Photosensitizing Agents - pharmacology; Photosensitizing Agents - therapeutic use; Protoporphyrin; Radiation; Radicals; Science; Science (multidisciplinary); Singlet Oxygen; Superoxide anions; Toxicity; Tumors; White light
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-29862-9

The most common working mechanism of photodynamic therapy is based on high-toxicity singlet oxygen, which is called Type II photodynamic therapy. But it is highly dependent on oxygen consumption. Recently, Type I photodynamic therapy has been found to have better hypoxia tolerance to ease this restriction. However, few strategies are available on the design of Type I photosensitizers. We herein report an unexpected strategy to alleviate the limitation of traditional photodynamic therapy by biotinylation of three photosensitizers (two fluorescein-based photosensitizers and the commercially available Protoporphyrin). The three biotiylated photosensitizers named as compound 1 , 2 and 3 , exhibit impressive ability in generating both superoxide anion radicals and singlet oxygen. Moreover, compound 1 can be activated upon low-power white light irradiation with stronger ability of anion radicals generation than the other two. The excellent combinational Type I / Type II photodynamic therapy performance has been demonstrated with the photosensitizers 1 . This work presents a universal protocol to provide tumor-targeting ability and enhance or trigger the generation of anion radicals by biotinylation of Type II photosensitizers against tumor hypoxia. Type I photodynamic therapy (PDT) sensitizers show good hypoxia tolerance but only few strategies are available for the design of purely organic Type I photosensitizers (PS). Here, the authors use biotinylation as design strategy to obtain PS-Biotin sensitizers with high efficiency for the generation of superoxide anion radicals and singlet oxygen.