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

详细信息    查看全文

• 作者：Jung Seung Nam ; Myeong-Gyun Kang ; Juhye Kang ; Sun-Young Park ; Shin Jung C. Lee ; Hyun-Tak Kim ; Jeong Kon Seo ; Oh-Hoon Kwon ; Mi Hee Lim ; Hyun-Woo Rhee ; Tae-Hyuk Kwon
• 刊名：Journal of the American Chemical Society
• 出版年：2016
• 出版时间：August 31, 2016
• 年：2016
• 卷：138
• 期：34
• 页码：10968-10977
• 全文大小：640K
• 年卷期：0
• ISSN：1520-5126

文摘

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.