In Vitro and In Vivo of Triphenylamine-Appended Fluorescent Half-Sandwich Iridium(III) Thiosemicarbazones Antitumor Complexes

Abstract

Half-sandwiched structure iridium­(III) complexes appear to be an attractive organometallic antitumor agents in recent years. Here, four triphenylamine-modified fluorescent half-sandwich iridium­(III) thiosemicarbazone (TSC) antitumor complexes were developed. Because of the “enol” configuration of the TSC ligands, these complexes formed a unique dimeric configuration. Aided by the appropriate fluorescence properties, studies found that complexes could enter tumor cells in an energy-dependent mode, accumulate in lysosomes, and result in the damage of lysosome integrity. Complexes could block the cell cycle, improve the levels of intrastitial reactive oxygen species, and lead to apoptosis, which followed an antitumor mechanism of oxidation. Compared with cisplatin, the antitumor potential in vivo and vitro confirmed that Ir4 could effectively inhibit tumor growth. Meanwhile, Ir4 could avoid detectable side effects in the experiments of safety evaluation. Above all, half-sandwich iridium­(III) TSC complexes are expected to be an encouraging candidate for the treatment of malignant tumors.

Single‐Cell Quantification of a Highly Biocompatible Dinuclear Iridium(III) Complex for Photocatalytic Cancer Therapy

“…To the best of our knowledge, such a high PI value with Ir III based photosensitizers is very rare. [5][6][7][8][9][10][11][12][13][14] It is important to note that the highest PI values reported with Ir III based photosensitizers are in the range of 8-250 (Table S6). [5][6][7][8][9][10][11][12][13][14] Thus, the PI value of Ir2 (ca.…”

“…[5][6][7][8][9][10][11][12][13][14] It is important to note that the highest PI values reported with Ir III based photosensitizers are in the range of 8-250 (Table S6). [5][6][7][8][9][10][11][12][13][14] Thus, the PI value of Ir2 (ca. 660 in HepG2 cells) is much higher than that of the other reported Ir IIIbased photosensitizers.…”

“…660 in HepG2 cells) is much higher than that of the other reported Ir IIIbased photosensitizers. [5][6][7][8][9][10][11][12][13][14] Moreover, PI values of Ir2 against A549 and A549/DDP cancer cells were ca. 36 and 80 respectively, again higher than for complexes reported in refs.…”

“…[4] It is important to mention that in recent years, several Ir III -based photosensitizers have been also developed for photoactivated cancer therapy. [5][6][7][8][9][10][11][12][13][14] These photosensitizers showed photo-triggered anticancer activity mainly via intracellular generation of reactive oxygen species (ROS). [5][6][7][8][9][10][11][12][13][14] Interestingly, Ir III -based complexes have also been reported for cancer diagnosis and imaging.…”

“…[5][6][7][8][9][10][11][12][13][14] These photosensitizers showed photo-triggered anticancer activity mainly via intracellular generation of reactive oxygen species (ROS). [5][6][7][8][9][10][11][12][13][14] Interestingly, Ir III -based complexes have also been reported for cancer diagnosis and imaging. [15] For example, Ma and co-workers have developed an Ir III complex to visualize β-galactosidase, the crucial biomarker for ovarian cancers.…”