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用于线粒体靶向光动力治疗的环金属化铱(III)配合物纳米颗粒

Cyclometalated iridium(iii) complex nanoparticles for mitochondria-targeted photodynamic therapy.

作者信息

Lu Huan, Jiang Xinpeng, Chen Yanyan, Peng Ke, Huang Yiming, Zhao Hao, Chen Qi, Lv Fengting, Liu Libing, Wang Shu, Ma Yuguo

机构信息

Beijing National Laboratory for Molecular Sciences, Center for Soft Matter Science and Engineering, Key Lab of Polymer Chemistry and Physics of the Ministry of Education, College of Chemistry, Peking University, Beijing, 100871, P. R. China.

出版信息

Nanoscale. 2020 Jul 14;12(26):14061-14067. doi: 10.1039/d0nr03398g. Epub 2020 Jun 25.

DOI:10.1039/d0nr03398g
PMID:32582896
Abstract

Cyclometalated Ir(iii) complexes, with a long triplet state lifetime and good photophysical properties, are good candidates for simultaneous imaging and photodynamic therapy (PDT). Herein, we synthesize a cyclometalated Ir(iii) complex, Ir(tiq)ppy, whose triplet excited state lifetime is 2.9 μs and singlet oxygen generation quantum yield is approximately 100% (compared to tetraphenylporphyrin). Ir(tiq)ppy nanoparticles (Ir(tiq)ppy NPs) are prepared to achieve water solubility and mitochondria-targeting ability by co-precipitating with polystyrene grafted with carboxyl-terminated poly(ethylene glycol) (PS-PEG). Ir(tiq)ppy NPs have higher PDT efficiency than Ir(tiq)ppy at concentrations as low as 1.6 μg mL for MCF-7 breast cancer cells under white light irradiation at quite low light intensity (5 mW cm). Besides, it is worth noting that the emission quenching of Ir(tiq)ppy in aqueous solution has been conquered by using Ir(tiq)ppy NPs, thus the distribution of the therapeutic agents in mitochondria can be tracked by confocal laser scanning microscopy (CLSM). The mechanism of killing cancer cells under irradiation is investigated, and the results indicate that cell death is caused by mitochondria-mediated apoptosis, which is induced by the ROS generated under light irradiation.

摘要

具有长三线态寿命和良好光物理性质的环金属化铱(III)配合物是同时进行成像和光动力疗法(PDT)的良好候选物。在此,我们合成了一种环金属化铱(III)配合物Ir(tiq)ppy,其三线态激发态寿命为2.9 μs,单线态氧生成量子产率约为100%(与四苯基卟啉相比)。通过与接枝有羧基封端聚乙二醇(PS-PEG)的聚苯乙烯共沉淀制备了Ir(tiq)ppy纳米颗粒(Ir(tiq)ppy NPs),以实现水溶性和线粒体靶向能力。在相当低的光强度(5 mW cm)的白光照射下,对于MCF-7乳腺癌细胞,Ir(tiq)ppy NPs在低至1.6 μg mL的浓度下比Ir(tiq)ppy具有更高的PDT效率。此外,值得注意的是,使用Ir(tiq)ppy NPs克服了Ir(tiq)ppy在水溶液中的发射猝灭,因此可以通过共聚焦激光扫描显微镜(CLSM)追踪治疗剂在线粒体中的分布。研究了照射下杀死癌细胞的机制,结果表明细胞死亡是由线粒体介导的凋亡引起的,而这种凋亡是由光照射下产生的活性氧(ROS)诱导的。

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