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.
CITATION STYLE
Nam, J. S., Kang, M. G., Kang, J., Park, S. Y., Lee, S. J. C., Kim, H. T., … Kwon, T. H. (2016). Endoplasmic Reticulum-Localized Iridium(III) Complexes as Efficient Photodynamic Therapy Agents via Protein Modifications. Journal of the American Chemical Society, 138(34), 10968–10977. https://doi.org/10.1021/jacs.6b05302
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