Molecular Design Strategy of the Efficient Generation of Reactive Oxygen Species and Their Protein Dysfunction Mechanism for Photodynamic Therapy

Abstract

Reactive oxygen species (ROS, 1O2, O2·, OH·, and H2O2) has known as one of the very important factors for biomedical applications, such as phototherapeutics for non-invasive therapy (photodynamic therapy; PDT) and wound healing hemostasis for fast cell recovery from serious injury or surgery. The controlling and understanding of ROS give insight into the clue of cell death mechanism or cell recovery by ROS, which will be helpful to overcome the chronical or pathogenic diseases like cancer or Alzheimer as well as aging. Until now, Ir(III) complexes have known as an efficient PDT photosensitizer because of their (i) high photostability, (ii) efficient triplet state utilization followed by (iii) high 1O2 quantum yield in aqueous media, and (iv) preference of hypoxia condition. However, there is no detailed molecular design strategy of ROS generation and the understanding of cell death mechanism by ROS. For this aim, our group have investigated on the Ir(III) complex based photosensitizers as well as organelle probes for the understanding of the interaction between proteins during the cell death. In this presentation, Ir(III) complexes based molecular design strategy will be presented for efficient ROS generation and their cell death mechanism based on proteomic analyses and phenomenological observations. In addition, we introduce a new 1O2 generator based on an aliphatic polyaminoglycerol (PAG), which relies on spin-flip electron transfer.