光动力疗法
化学
癌症研究
超氧化物
癌细胞
生物物理学
激进的
细胞凋亡
体内
癌症
生物化学
医学
生物
内科学
酶
有机化学
生物技术
作者
Mingle Li,Jing Xia,Ruixue Tian,Jingyun Wang,Jiangli Fan,Jianjun Du,Saran Long,Xiangzhi Song,James W. Foley,Xiaojun Peng
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 (O2–•) generator (ENBS-B) to surmount this intractable issue, also reveal its detailed O2–• action mechanism underlying the antihypoxia effects, and confirm its application for in vivo targeted hypoxic solid tumor ablation. Photomediated radical generation mechanism study shows that, even under severe hypoxic environment (2% O2), ENBS-B can generate considerable O2–• through type I photoreactions, and partial O2–• 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 cancer therapy.
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