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个人信息Personal Information
教授
博士生导师
硕士生导师
主要任职：Director, State Key laboratory of Fine Chemicals
其他任职：精细化工国家重点实验室主任、国务院学科评议组成员
性别：男
毕业院校：大连理工大学
学位：博士
所在单位：化工学院
学科：应用化学. 精细化工. 化学生物学
办公地点：大连理工大学精细化工国家重点实验室
西部校区化工实验楼F-202#
http://peng-group.dlut.edu.cn/
联系方式：大连理工大学精细化工国家重点实验室 西部校区化工实验楼F-202 辽宁省大连市高新区凌工路2号，大连116024 Tel: 0411-84986306; Fax: 0411-84986292；课题组网址：http://peng-group.dlut.edu.cn/
电子邮箱：pengxj@dlut.edu.cn
Near-Infrared Light-Initiated Molecular Superoxide Radical Generator: Rejuvenating Photodynamic Therapy against Hypoxic Tumors
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论文类型：期刊论文
发表时间：2021-01-30
发表刊物：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷号：140
期号：44
页面范围：14851-14859
ISSN号：0002-7863
关键字：Cell death; Diseases; Infrared devices; Tumors, Cancer cell apoptosis; Hypoxic environments; Intravenous administration; Near infrared light; Personalized medicines; Photodynamic therapy (PDT); Radical generation mechanisms; Therapeutic efficacy, Photodynamic therapy, antineoplastic agent; biotin; oxygen; superoxide, antihypoxia activity; apoptosis; Article; cancer cell; cancer inhibition; cancer tissue; cell transport; coculture; disease severity; dose response; drug activity; drug cytotoxicity; drug synthesis; human; in vitro study; in vivo study; ligand binding; neoplasm; nonhuman; patent; personalized medicine; photodynamic therapy; photoreactivity; radiation dose; rejuvenation; tumor ablation; tumor hypoxia
摘要：Hypoxia, a quite universal feature in most solid tumors, has been considered as the "Achilles' heel" of traditional photodynamic therapy (PDT) and substantially impairs the overall therapeutic efficacy. Herein, we develop a near-infrared (NIR) light-triggered molecular superoxide radical (O-2(-center dot)) generator (ENBS-B) to surmount this intractable issue, also reveal its detailed O-2(-center dot) action mechanism underlying the antihypoxia effects, and confirm its application for in vivo targeted hypoxic solid tumor ablation. Photo mediated radical generation mechanism study shows that, even under severe hypoxic environment (2% O-2), ENBS-B can generate considerable O-2(-center dot) through type I photoreactions, and partial O-2(-center dot) is transformed to high toxic OH. through SOD mediated cascade reactions. These radicals synergistically damage the intracellular lysosomes, which subsequently trigger cancer cell apoptosis, presenting a robust hypoxic PDT potency. In vitro coculture model shows that, benefiting from biotin ligand, ENBS-B achieves 87-fold higher cellular uptake in cancer cells than normal cells, offering opportunities for personalized medicine. Following intravenous administration, ENBS-B is able to specifically target to neoplastic tissues and completely suppresses the tumor growth at a low light-dose irradiation. As such, we postulated this work will extend the options of excellent agents for clinical