Issue 31, 2024

Cyclometalated iridium(iii) tetrazine complexes for mitochondria-targeted two-photon photodynamic therapy

Abstract

The fast-moving field of photodynamic therapy (PDT) has provided fresh opportunities to expand the potential of metallodrugs to combat cancers in a light-controlled manner. As such, in the present study, a series of cyclometalated Ir(III) complexes modified with a tetrazine functional group (namely, Ir-ppy-Tz, Ir-pbt-Tz, and Ir-dfppy-Tz) are developed as potential two-photon photodynamic anticancer agents. These complexes target mitochondria but exhibit low toxicity towards HLF primary lung fibroblast normal cells in the dark. When receiving a low-dose one- or two-photon PDT, they become highly potent towards A549 lung cancer cells (with IC50 values ranging from 24.0 nM to 96.0 nM) through the generation of reactive oxygen species (ROS) to induce mitochondrial damage and subsequent apoptosis. Our results indicated that the incorporation of tetrazine with cyclometalated Ir(III) matrices would increase the singlet oxygen (1O2) quantum yield (ΦΔ) and, meanwhile, enable a type I PDT mechanism. Ir-pbt-Tz, with the largest two-photon absorption (TPA) cross-section (σ2 = 102 GM), shows great promise in serving as a two-photon PDT agent for phototherapy.

Graphical abstract: Cyclometalated iridium(iii) tetrazine complexes for mitochondria-targeted two-photon photodynamic therapy

Supplementary files

Article information

Article type
Paper
Submitted
08 Jun 2024
Accepted
12 Jul 2024
First published
12 Jul 2024

Dalton Trans., 2024,53, 12917-12926

Cyclometalated iridium(III) tetrazine complexes for mitochondria-targeted two-photon photodynamic therapy

Z. Tan, M. Lin, J. Liu, H. Wu and H. Chao, Dalton Trans., 2024, 53, 12917 DOI: 10.1039/D4DT01665C

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