Photodynamic therapy(PDT)holds significant promise as a medical treatment approach in human diseases.Recently,PDT has received attention to harness light-induced reactive oxygen species and,subsequently,modify amyloid...Photodynamic therapy(PDT)holds significant promise as a medical treatment approach in human diseases.Recently,PDT has received attention to harness light-induced reactive oxygen species and,subsequently,modify amyloidogenic peptides implicated in human degenerative diseases.Here we report a series of strategically designed photosensitizers comprised of boron-dipyrromethene(BODIPY)scaffolds conjugated with transition metal ions.Our comprehensive biophysical and biochemical investigations demonstrate the efficacy of the photosensitizers in generating reactive oxygen species(ROS),such as singlet oxygen(^(1)O_(2)),superoxide anion radicals(O_(2)^(·-)),and hydroxyl radicals(·OH),upon photoactivation at a relatively longer wavelength,resulting in the oxidation of amyloid-β(Aβ).Consequently,the induced oxidation brings about significant alterations in the aggregation pathways and morphologies of the peptides.Moreover,Aβspecies produced by treating the metal complex,Ir-BDP,exhibiting the highest ROS generation efficiency and photoactivation,are less toxic than the complex-free Aβspecies.Overall,our findings underscore the therapeutic potential of these newly designed photosensitizers in addressing amyloid-related diseases.展开更多
基金work was supported by the National Research Foundation of Korea(NRF)grant funded by the Korean government[NRF-2022R1I1A1A01064065(G.G.)NRF-2022R1A3B1077319(M.H.L.)+2 种基金NRF-2021R1A2C1011731(C.Y.L.)NRF-2022R1A2C1011793(Y.-H.L.)]the Sejong Science Fellowship Grants(RS-2023-00214034).
文摘Photodynamic therapy(PDT)holds significant promise as a medical treatment approach in human diseases.Recently,PDT has received attention to harness light-induced reactive oxygen species and,subsequently,modify amyloidogenic peptides implicated in human degenerative diseases.Here we report a series of strategically designed photosensitizers comprised of boron-dipyrromethene(BODIPY)scaffolds conjugated with transition metal ions.Our comprehensive biophysical and biochemical investigations demonstrate the efficacy of the photosensitizers in generating reactive oxygen species(ROS),such as singlet oxygen(^(1)O_(2)),superoxide anion radicals(O_(2)^(·-)),and hydroxyl radicals(·OH),upon photoactivation at a relatively longer wavelength,resulting in the oxidation of amyloid-β(Aβ).Consequently,the induced oxidation brings about significant alterations in the aggregation pathways and morphologies of the peptides.Moreover,Aβspecies produced by treating the metal complex,Ir-BDP,exhibiting the highest ROS generation efficiency and photoactivation,are less toxic than the complex-free Aβspecies.Overall,our findings underscore the therapeutic potential of these newly designed photosensitizers in addressing amyloid-related diseases.
