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-β (Aβ). Consequently, the induced oxidation brings about significant alterations in the aggregation pathways and morphologies of the peptides. Moreover, Aβ species produced by treating the metal complex, Ir-BDP, exhibiting the highest ROS generation efficiency and photoactivation, are less toxic than the complex-free Aβ species. Overall, our findings underscore the therapeutic potential of these newly designed photosensitizers in addressing amyloid-related diseases.