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Synthesis, photophysical and anticancer properties of mitochondria-targeted phosphorescent cyclometalated iridium(III) N-heterocyclic carbene complexes.
Journal of Inorganic Biochemistry ( IF 3.8 ) Pub Date : 2019-12-27 , DOI: 10.1016/j.jinorgbio.2019.110976
Yi Li 1 , Kang-Nan Wang 2 , Liang He 3 , Liang-Nian Ji 2 , Zong-Wan Mao 2
Journal of Inorganic Biochemistry ( IF 3.8 ) Pub Date : 2019-12-27 , DOI: 10.1016/j.jinorgbio.2019.110976
Yi Li 1 , Kang-Nan Wang 2 , Liang He 3 , Liang-Nian Ji 2 , Zong-Wan Mao 2
Affiliation
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Metal N-Heterocyclic carbene (NHC) complexes are expected to be new opportunities for the development of anticancer metallodrugs. In this work, two near-infrared (NIR) emitting iridium(III)-NHC complexes Ir1 and Ir2 have been explored as mitochondria-targeted anticancer and photodynamic agents. These complexes are more cytotoxic than cisplatin against the cancer cells screened, and display higher cytotoxicity in the presence of 450 nm and 630 nm LED light. Colocalization and quantitative studies indicated that these complexes could specially localize to mitochondria. Mechanism studies show that these complexes increase intracellular reactive oxygen species (ROS) level, reduce mitochondrial membrane potential (MMP) and induce some degree of early apoptosis. Further studies found that Ir1could induce mitophagy at dark and necrocytosis under the irradiation of 630 nm LED light. The in vitro and in vivo photoxicity studies revealed that Ir1 is a promising photodynamic therapy (PDT) agent and could significantly inhibit tumor growth.
中文翻译：
线粒体靶向的磷光环金属化铱（III）N-杂环卡宾配合物的合成，光物理和抗癌性能。
金属N-杂环卡宾（NHC）配合物有望成为开发抗癌金属药物的新机会。在这项工作中，已经探索了两种发射近红外（NIR）的铱（III）-NHC复合物Ir1和Ir2作为靶向线粒体的抗癌剂和光动力剂。这些复合物比顺铂对筛选的癌细胞更具细胞毒性，并且在450 nm和630 nm LED光的情况下显示出更高的细胞毒性。共定位和定量研究表明，这些复合物可以专门定位于线粒体。机理研究表明，这些复合物可增加细胞内活性氧（ROS）水平，降低线粒体膜电位（MMP）并诱导一定程度的早期凋亡。进一步的研究发现，Ir1可以在630 nm LED灯的照射下在黑暗中诱导线粒体吞噬和坏死。体外和体内光毒性研究表明，Ir1是一种有前途的光动力疗法（PDT）药物，可以显着抑制肿瘤的生长。
更新日期：2019-12-27
中文翻译：
线粒体靶向的磷光环金属化铱（III）N-杂环卡宾配合物的合成，光物理和抗癌性能。
金属N-杂环卡宾（NHC）配合物有望成为开发抗癌金属药物的新机会。在这项工作中，已经探索了两种发射近红外（NIR）的铱（III）-NHC复合物Ir1和Ir2作为靶向线粒体的抗癌剂和光动力剂。这些复合物比顺铂对筛选的癌细胞更具细胞毒性，并且在450 nm和630 nm LED光的情况下显示出更高的细胞毒性。共定位和定量研究表明，这些复合物可以专门定位于线粒体。机理研究表明，这些复合物可增加细胞内活性氧（ROS）水平，降低线粒体膜电位（MMP）并诱导一定程度的早期凋亡。进一步的研究发现，Ir1可以在630 nm LED灯的照射下在黑暗中诱导线粒体吞噬和坏死。体外和体内光毒性研究表明，Ir1是一种有前途的光动力疗法（PDT）药物，可以显着抑制肿瘤的生长。
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