Synthesis of Mitochondria-Anchored Nitroimidazoles with a Versatile NIR Fluorophore for Hypoxic Tumor-Targeting Imaging and Chemoradiotherapy

被引：34

作者：

Chen, Sha ^{[1
,2
]}

Yu, Songtao ^{[3
]}

Du, Zaizhi ^{[1
]}

Huang, Xie ^{[1
]}

He, Meng ^{[2
]}

Long, Shuang ^{[1
]}

Liu, Jing ^{[1
]}

Lan, Yu ^{[4
]}

Yang, Dong ^{[4
]}

Wang, Hao ^{[4
]}

Li, Shuhui ^{[2
]}

Chen, An ^{[2
]}

Hao, Yuhui ^{[1
]}

Su, Yongping ^{[1
]}

Wang, Changning ^{[4
]}

Luo, Shenglin ^{[1
]}

机构：

[1] Third Mil Med Univ Army Med Univ, State Key Lab Trauma Burns & Combined Injury, Inst Combined Injury, Chongqing Engn Res Ctr Nanomed,Coll Prevent Med, Chongqing 400038, Peoples R China

[2] Third Mil Med Univ Army Med Univ, Dept Clin Biochem, Lab Sci, Chongqing 400038, Peoples R China

[3] Third Mil Med Univ Army Med Univ, Southwest Hosp, Dept Oncol, Chongqing 400038, Peoples R China

[4] Harvard Med Sch, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Charlestown, MA 02129 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2021年 / 64卷 / 06期

基金：

中国国家自然科学基金;

关键词：

CANCER; DYE; PROBE; RESISTANCE; DIAGNOSIS;

D O I：

10.1021/acs.jmedchem.0c02250

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Nitroimidazoles are one of the most common radiosensitizers investigated to combat hypoxia-induced resistance to cancer radiotherapy. However, due to poor selectivity distinguishing cancer cells from normal cells, effective doses of radiosensitization are much closer to the doses of toxicity induced by nitroimidazoles, limiting their clinical application. In this work, a tumor-targeting near-infrared (NIR) cyanine dye (IR-808) was utilized as a targeting ligand and an NIR fluorophore tracer to chemically conjugate with different structures of hypoxia-affinic nitroimidazoles. One of the NIR fluorophore-conjugated nitroimidazoles (808-NM2) was identified to preferentially accumulate in hypoxic tumor cells, sensitively outline the tumor contour, and effectively inhibit tumor growth synergistically by chemotherapy and radiotherapy. More importantly, nitroimidazoles were successfully taken into cancer cell mitochondria via 808-NM2 conjugate to exert the synergistic effect of chemoradiotherapy. Regarding the important roles of mitochondria on cancer cell survival and metastasis under hypoxia, 808-NM2 may be hopeful to fight against hypoxic tumors.

引用

页码：3381 / 3391

页数：11

共 35 条

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