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J Am Chem Soc. 2016 Aug 31;138(34):10968-77. doi: 10.1021/jacs.6b05302. Epub 2016 Aug 22.

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

Author information

1
Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST) , Ulsan 44919, Republic of Korea.
2
Center for Soft and Living Matter, Institute for Basic Science (IBS) , Ulsan 44919, Republic of Korea.
3
UNIST Central Research Facility, Ulsan National Institute of Science and Technology (UNIST) , Ulsan 44919, Republic of Korea.

Abstract

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.

PMID:
27494510
DOI:
10.1021/jacs.6b05302
[Indexed for MEDLINE]

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