Mitochondria-targeted iridium-based photosensitizers enhancing photodynamic therapy effect by disturbing cellular redox balance

Miao Zhong; Jian He; Baoxin Zhang; Qiang Liu; Jianguo Fang

doi:10.1016/j.freeradbiomed.2022.12.091

Mitochondria-targeted iridium-based photosensitizers enhancing photodynamic therapy effect by disturbing cellular redox balance

Free Radic Biol Med. 2023 Feb 1:195:121-131. doi: 10.1016/j.freeradbiomed.2022.12.091. Epub 2022 Dec 26.

Authors

Miao Zhong¹, Jian He², Baoxin Zhang¹, Qiang Liu³, Jianguo Fang⁴

Affiliations

¹ The State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu, 730000, China.
² The State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu, 730000, China; Sichuan Key Laboratory of Medical Imaging, School of Medical Imaging, North Sichuan Medical College, Nanchong, 637000, China.
³ The State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu, 730000, China. Electronic address: liuqiang@lzu.edu.cn.
⁴ The State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu, 730000, China; School of Chemistry and Chemical Engineering, Nanjing University of Science & Technology, Nanjing, Jiangsu, 210094, China. Electronic address: fangjg@lzu.edu.cn.

PMID: 36581057
DOI: 10.1016/j.freeradbiomed.2022.12.091

Abstract

Photodynamic therapy (PDT) is a non-invasive, light-activated treatment approach that has been broadly employed in cancer. Cyclometallic iridium (Ш) complexes are candidates for ideal photosensitizers due to their unique photophysical and photochemical features, such as high quantum yield, large Stokes shift, strong resistance to photobleaching, and high cellular permeability. We evaluated a panel of iridium complexes and identified PC9 as a powerful photosensitizer to kill cancer cells. PC9 shows an 8-fold increase of cytotoxicity to HeLa cells under light irradiation. Further investigation discloses that PC9 has a strong mitochondrial-targeting ability and can inhibit the antioxidant enzyme thioredoxin reductase, which contributes to improving PDT efficacy. Our data indicate that iridium complexes are efficient photosensitizers with distinct physicochemical properties and cellular actions, and deserve further development as promising agents for PDT.

Keywords: Iridium (III) complex; Photodynamic therapy; Reactive oxygen species; Redox metabolism; Thioredoxin reductase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

HeLa Cells
Humans
Iridium / chemistry
Iridium / pharmacology
Mitochondria
Oxidation-Reduction
Photochemotherapy*
Photosensitizing Agents* / chemistry

Substances

Photosensitizing Agents
Iridium