Metal-BODIPY complexes: versatile photosensitizers for oxidizing amyloid-β peptides and modulating their aggregation profiles

Abstract

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 (1O2), superoxide anion radicals (O2-), and hydroxyl radicals (OH), upon photoactivation at a relatively longer wavelength, resulting in the oxidation of amyloid-beta (A beta). Consequently, the induced oxidation brings about significant alterations in the aggregation pathways and morphologies of the peptides. Moreover, A beta species produced by treating the metal complex, Ir-BDP, exhibiting the highest ROS generation efficiency and photoactivation, are less toxic than the complex-free A beta species. Overall, our findings underscore the therapeutic potential of these newly designed photosensitizers in addressing amyloid-related diseases.,Metal-BODIPY complexes, rationally designed as photosensitizers, can effectively oxidize amyloidogenic peptides upon photoactivation at a relatively longer wavelength, resulting in altering their aggregation profiles.,