Endoplasmic Reticulum-Localized Iridium(III) Complexes as Efficient Photodynamic Therapy Agents via Protein Modifications.

Citation data:

Journal of the American Chemical Society, ISSN: 1520-5126, Vol: 138, Issue: 34, Page: 10968-77

Publication Year:
2016
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Repository URL:
http://scholarworks.unist.ac.kr/handle/201301/20462
PMID:
27494510
DOI:
10.1021/jacs.6b05302
Author(s):
Nam, Jung Seung; Kang, Myeong-Gyun; Kang, Juhye; Park, Sun-Young; Lee, Shin Jung C; Kim, Hyun-Tak; Seo, Jeong Kon; Kwon, Oh-Hoon; Lim, Mi Hee; Rhee, Hyun-Woo; Kwon, Tae-Hyuk Show More Hide
Publisher(s):
American Chemical Society (ACS); AMER CHEMICAL SOC
Tags:
Chemical Engineering; Chemistry; Biochemistry, Genetics and Molecular Biology
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article description
Protein inactivation by reactive oxygen species (ROS) such as singlet oxygen ((1)O2) and superoxide radical (O2(•-)) is considered to trigger cell death pathways associated with protein dysfunction; however, the detailed mechanisms and direct involvement in photodynamic therapy (PDT) have not been revealed. Herein, we report Ir(III) complexes designed for ROS generation through a rational strategy to investigate protein modifications by ROS. The Ir(III) complexes are effective as PDT agents at low concentrations with low-energy irradiation (≤ 1 J cm(-2)) because of the relatively high (1)O2 quantum yield (> 0.78), even with two-photon activation. Furthermore, two types of protein modifications (protein oxidation and photo-cross-linking) involved in PDT were characterized by mass spectrometry. These modifications were generated primarily in the endoplasmic reticulum and mitochondria, producing a significant effect for cancer cell death. Consequently, we present a plausible biologically applicable PDT modality that utilizes rationally designed photoactivatable Ir(III) complexes.