A Mitochondria-Targeted Photosensitizer Showing Improved Photodynamic Therapy Effects Under Hypoxia

被引:464
作者
Lv, Wen [1 ,2 ]
Zhang, Zhang [1 ,2 ]
Zhang, Kenneth Yin [1 ,2 ]
Yang, Huiran [1 ,2 ]
Liu, Shujuan [1 ,2 ]
Xu, Aqiang [1 ,2 ]
Guo, Song [1 ,2 ]
Zhao, Qiang [1 ,2 ]
Huang, Wei [1 ,2 ,3 ,4 ]
机构
[1] NUPT, Jiangsu Natl Synerget Innovat Ctr Adv Mat SICAM, Key Lab Organ Elect & Informat Displays, Nanjing 210023, Jiangsu, Peoples R China
[2] NUPT, Jiangsu Natl Synerget Innovat Ctr Adv Mat SICAM, Inst Adv Mat, Nanjing 210023, Jiangsu, Peoples R China
[3] Nanjing Tech Univ NanjingTech, Jiangsu Natl Synerget Innovat Ctr Adv Mat SICAM, Key Lab Flexible Elect KLOFE, Nanjing 211816, Jiangsu, Peoples R China
[4] Nanjing Tech Univ NanjingTech, Jiangsu Natl Synerget Innovat Ctr Adv Mat SICAM, Inst Adv Mat, Nanjing 211816, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
cell death; hypoxia; iridium; photodynamic therapy; singlet oxygen; PHOTOINDUCED CELL-DEATH; CANCER-THERAPY; PHOTOCHEMICAL PROPERTIES; POLYPYRIDYL COMPLEXES; IRIDIUM(III) COMPLEX; EXCITED-STATES; NANOPARTICLES; LIGAND; TRAFFICKING; INHIBITION;
D O I
10.1002/anie.201604130
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Organelle-targeted photosensitizers have been reported to be effective photodynamic therapy (PDT) agents. In this work, we designed and synthesized two iridium(III) complexes that specifically stain the mitochondria and lysosomes of living cells, respectively. Both complexes exhibited long-lived phosphorescence, which is sensitive to oxygen quenching. The photocytotoxicity of the complexes was evaluated under normoxic and hypoxic conditions. The results showed that HeLa cells treated with the mitochondria-targeted complex maintained a slower respiration rate, leading to a higher intracellular oxygen level under hypoxia. As a result, this complex exhibited an improved PDT effect compared to the lysosome-targeted complex, especially under hypoxia conditions, suggestive of a higher practicable potential of mitochondria-targeted PDT agents in cancer therapy.
引用
收藏
页码:9947 / 9951
页数:5
相关论文
共 34 条
[1]   Marked Improvement in Photoinduced Cell Death by a New Tris-heteroleptic Complex with Dual Action: Singlet Oxygen Sensitization and Ligand Dissociation [J].
Albani, Bryan A. ;
Pena, Bruno ;
Leed, Nicholas A. ;
de Paula, Nataly A. B. G. ;
Pavani, Christiane ;
Baptista, Mauricio S. ;
Dunbar, Kim R. ;
Turro, Claudia .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2014, 136 (49) :17095-17101
[2]  
[Anonymous], 2015, ANGEW CHEM, V127, P14255
[3]  
[Anonymous], 2012, ANGEW CHEM, V124, P11584
[4]  
Bertram John S., 2000, Molecular Aspects of Medicine, V21, P167, DOI 10.1016/S0098-2997(00)00007-8
[5]   Oxygen atom transfer from nitrogenous ReVO reagents to diphosphines and subsequent transformations.: Rhenium(III) products and reaction models [J].
Bhattacharyya, S ;
Chakraborty, I ;
Dirghangi, BK ;
Chakravorty, A .
INORGANIC CHEMISTRY, 2001, 40 (02) :286-293
[6]   Imaging and Photodynamic Therapy: Mechanisms, Monitoring, and Optimization [J].
Celli, Jonathan P. ;
Spring, Bryan Q. ;
Rizvi, Imran ;
Evans, Conor L. ;
Samkoe, Kimberley S. ;
Verma, Sarika ;
Pogue, Brian W. ;
Hasan, Tayyaba .
CHEMICAL REVIEWS, 2010, 110 (05) :2795-2838
[7]   Perfluorocarbon nanoparticles enhance reactive oxygen levels and tumour growth inhibition in photodynamic therapy [J].
Cheng, Yuhao ;
Cheng, Hao ;
Jiang, Chenxiao ;
Qiu, Xuefeng ;
Wang, Kaikai ;
Huan, Wei ;
Yuan, Ahu ;
Wu, Jinhui ;
Hu, Yiqiao .
NATURE COMMUNICATIONS, 2015, 6
[8]   Photoactivated chemotherapy (PACT): the potential of excited-state d-block metals in medicine [J].
Farrer, Nicola J. ;
Salassa, Luca ;
Sadler, Peter J. .
DALTON TRANSACTIONS, 2009, (48) :10690-10701
[9]   Targeting mitochondria for cancer therapy [J].
Fulda, Simone ;
Galluzzi, Lorenzo ;
Kroemer, Guido .
NATURE REVIEWS DRUG DISCOVERY, 2010, 9 (06) :447-464
[10]   The pathophysiology of mitochondrial cell death [J].
Green, DR ;
Kroemer, G .
SCIENCE, 2004, 305 (5684) :626-629