title: Endoplasmic Reticulum-Localized Iridium(III) Complexes as Efficient Photodynamic Therapy Agents via Protein Modifications.
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.
authors: Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST) , Ulsan 44919, Republic of Korea.
authors: Jung Seung
authors: JS
authors: Nam
authors: Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST) , Ulsan 44919, Republic of Korea.
authors: Myeong-Gyun
authors: MG
authors: Kang
authors: Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST) , Ulsan 44919, Republic of Korea.
authors: Juhye
authors: J
authors: Kang
authors: Center for Soft and Living Matter, Institute for Basic Science (IBS) , Ulsan 44919, Republic of Korea.
authors: Sun-Young
authors: SY
authors: Park
authors: Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST) , Ulsan 44919, Republic of Korea.
authors: Shin Jung C
authors: SJ
authors: Lee
authors: Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST) , Ulsan 44919, Republic of Korea.
authors: Hyun-Tak
authors: HT
authors: Kim
authors: UNIST Central Research Facility, Ulsan National Institute of Science and Technology (UNIST) , Ulsan 44919, Republic of Korea.
authors: Jeong Kon
authors: JK
authors: Seo
authors: Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST) , Ulsan 44919, Republic of Korea.|Center for Soft and Living Matter, Institute for Basic Science (IBS) , Ulsan 44919, Republic of Korea.
authors: Oh-Hoon
authors: OH
authors: Kwon
authors: Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST) , Ulsan 44919, Republic of Korea.
authors: Mi Hee
authors: MH
authors: Lim
authors: Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST) , Ulsan 44919, Republic of Korea.
authors: Hyun-Woo
authors: HW
authors: Rhee
authors: Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST) , Ulsan 44919, Republic of Korea.
authors: Tae-Hyuk
authors: TH
authors: Kwon
mesh_terms: D001692:Biological Transport; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007495:Iridium / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism*; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000378:metabolism*; D026082:Singlet Oxygen / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000378:metabolism*
chemical_list: D009942:Organometallic Compounds; D017319:Photosensitizing Agents; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D026082:Singlet Oxygen; D007495:Iridium