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氮氧化物和氢自由基的级联反应在可激活光敏剂抗缺氧光动力治疗中的应用
作者:小柯机器人 发布时间:2021/1/13 15:50:23

中国科学院化学研究所王树团队报道了氮氧化物和氢自由基的级联反应在可激活光敏剂抗缺氧光动力治疗中的应用。 相关研究成果于2021年1月8日发表在《美国化学会志》。

以细胞器为靶点的可激活光敏剂对提高光动力疗法(PDT)的特异性和可控性很有吸引力,但由于光毒性物质(主要是活性氧物质)的多样性有限,它们在常氧和缺氧条件下的光活性都存在很大的问题。

该文中,研究人员通过用N-亚硝胺取代基有效地光老化π-共轭供体-受体(D–A)结构,建立了单分子谷胱甘肽和光共激活光敏剂,通过Ⅰ型和Ⅱ型(双型)反应以及二次自由基参与反应靶向线粒体,实现了高效的PDT效应。特别有趣的是,通过电子自旋共振技术检测到了氢自由基(H)。文章讨论了质子还原生成氢自由基的途径及其在Ⅰ型反应中的作用。

研究人员证明了多个反应物种的协同效应起源于串联级联反应,包括O2被H还原形成O2–/HO2和O2与NO的下游反应生成ONOO–。这种新型光敏剂具有在近红外光激发(800nm处为166±22GM)较大的双光子吸收截面和荧光性质,在常氧和低氧环境下具有广泛的生物医学应用前景,特别是在低光剂量PDT中。

附:英文原文

Title: Cascade Reactions by Nitric Oxide and Hydrogen Radical for Anti-Hypoxia Photodynamic Therapy Using an Activatable Photosensitizer

Author: Jian Sun, Xuetong Cai, Chengjun Wang, Ke Du, Weijian Chen, Fude Feng, Shu Wang

Issue&Volume: January 8, 2021

Abstract: Organelle-targeted activatable photosensitizers are attractive to improve the specificity and controllability of photodynamic therapy (PDT), however, they suffer from a big problem in the photoactivity under both normoxia and hypoxia due to the limited diversity of phototoxic species (mainly reactive oxygen species). Herein, by effectively photocaging a π-conjugated donor–acceptor (D–A) structure with an N-nitrosamine substituent, we established a unimolecular glutathione and light coactivatable photosensitizer, which achieved its high performance PDT effect by targeting mitochondria through both type I and type II (dual type) reactions as well as secondary radicals-participating reactions. Of peculiar interest, hydrogen radical (H) was detected by electron spin resonance technique. The generation pathway of H via reduction of proton and its role in type I reaction were discussed. We demonstrated that the synergistic effect of multiple reactive species originated from tandem cascade reactions comprising reduction of O2 by H to form O2–/HO2 and downstream reaction of O2– with NO to yield ONOO–. With a relatively large two-photon absorption cross section for photoexcitation in the near-infrared region (166 ± 22 GM at 800 nm) and fluorogenic property, the new photosensitizing system is very promising for broad biomedical applications, particularly low-light dose PDT, in both normoxic and hypoxic environments.

DOI: 10.1021/jacs.0c10517

Source: https://pubs.acs.org/doi/10.1021/jacs.0c10517

 

期刊信息

JACS:《美国化学会志》,创刊于1879年。隶属于美国化学会,最新IF:14.612
官方网址:https://pubs.acs.org/journal/jacsat
投稿链接:https://acsparagonplus.acs.org/psweb/loginForm?code=1000