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Anticancer Ir III –Aspirin Conjugates for Enhanced Metabolic Immuno‐Modulation and Mitochondrial Lifetime Imaging
Author(s) -
Wu XiaoWen,
Zheng Yue,
Wang FangXin,
Cao JianJun,
Zhang Hang,
Zhang DongYang,
Tan CaiPing,
Ji LiangNian,
Mao ZongWan
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201900851
Subject(s) - chemistry , aspirin , cancer research , apoptosis , salicylic acid , mitochondrion , in vivo , phosphorescence , pharmacology , biochemistry , biology , fluorescence , physics , microbiology and biotechnology , quantum mechanics
The chemo‐anti‐inflammatory strategy is attracting ever more attention for the treatment of cancer. Here, two cyclometalated Ir III complexes Ir2 and Ir3 formed by conjugation of Ir1 with two antiphlogistics (aspirin and salicylic acid) have been designed. Ir2 and Ir3 exhibit higher antitumor and anti‐inflammatory potencies than a mixture of Ir1 and aspirin/salicylic acid. We show that they can be hydrolyzed, accumulate in mitochondria, and induce mitochondrial dysfunction. Due to their intense long‐lived phosphorescence, Ir2 and Ir3 can track mitochondrial morphological changes. Phosphorescence lifetime imaging shows that Ir2 and Ir3 can aggregate during mitochondrial dysfunction. As expected, Ir2 and Ir3 exhibit immunomodulatory properties by regulating the activity of immune factors. Both Ir2 and Ir3 can induce caspase‐dependent apoptosis and caspase‐independent paraptosis and inhibit several events related to metastasis. Moreover, Ir2 and Ir3 show potent tumor growth inhibition in vivo. Our study demonstrates that the combination of mitochondrial‐targeting and immunomodulatory activities is feasible to develop multifunctional metal‐based anticancer agents.