单线态氧
光动力疗法
化学
铱
前药
光敏剂
线粒体
活性氧
癌症研究
癌细胞
生物物理学
组合化学
缺氧(环境)
光毒性
光化学
癌症
体外
氧气
生物化学
催化作用
有机化学
内科学
生物
医学
作者
Shi Kuang,Fangmian Wei,Johannes Karges,Libing Ke,Kai Xiong,Xinxing Liao,Gilles Gasser,Liang‐Nian Ji,Hui Chao
摘要
Despite the clinical success of photodynamic therapy (PDT), the application of this medical technique is intrinsically limited by the low oxygen concentrations found in cancer tumors, hampering the production of therapeutically necessary singlet oxygen (1O2). To overcome this limitation, we report on a novel mitochondria-localized iridium(III) endoperoxide prodrug (2-O-IrAn), which, upon two-photon irradiation in NIR, synergistically releases a highly cytotoxic iridium(III) complex (2-IrAn), singlet oxygen, and an alkoxy radical. 2-O-IrAn was found to be highly (photo-)toxic in hypoxic tumor cells and multicellular tumor spheroids (MCTS) in the nanomolar range. To provide cancer selectivity and improve the pharmacological properties of 2-O-IrAn, it was encapsulated into a biotin-functionalized polymer. The generated nanoparticles were found to nearly fully eradicate the tumor inside a mouse model within a single treatment. This study presents, to the best of our knowledge, the first example of an iridium(III)-based endoperoxide prodrug for synergistic photodynamic therapy/photoactivated chemotherapy, opening up new avenues for the treatment of hypoxic tumors.
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