Endoplasmic Reticulum-Localized Iridium(III) Complexes as Efficient Photodynamic Therapy Agents via Protein Modifications
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- Endoplasmic Reticulum-Localized Iridium(III) Complexes as Efficient Photodynamic Therapy Agents via Protein Modifications
- 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
- Issue Date
- AMER CHEMICAL SOC
- JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, v.138, no.34, pp.10968 - 10977
- Protein inactivation by reactive oxygen species (ROS) such as singlet oxygen (1O2) 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 1O2 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.
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