Application of PEG-modified Copper-cysteamine in photodynamic therapy for Alzheimer's disease

Abstract

• The Cu-Cy and Cu-Cy-PEG were synthetized, and the biosafety of Cu-Cy-PEG was improved. • Cu-Cy-PEG can generate ROS efficiently and be used to degrade Aβ aggregates. • The beta-sheet secondary structure of amyloid fibrils was destroyed in PDT. As a progressive neurodegenerative disease, Alzheimer's disease (AD) is characterized by the accumulation and misfolding of amyloid polypeptides (Aβ) which results in irreversible brain damages, cognitive decline and behavioral impairment. Photodynamic therapy (PDT) has received much attention as a potential approach for AD treatment. In this study, we investigated a novel multifunctional photosensitizer, copper-cysteamine (Cu-Cy). With PEG modification on the surface (Cu-Cy-PEG), the particle size and cytotoxicity of Cu-Cy-PEG were significantly reduced compared with Cu-Cy. Under UV irradiation, Cu-Cy-PEG can produce reactive oxygen species (ROS) and could degrade Aβ(1-40) aggregates efficiently. The macroscopic amyloid aggregates were photodegraded by Cu-Cy-PEG into amorphous particles. This is the first case for Cu-Cy-PEG being used for degrading Aβ aggregates in vitro, which proved that Cu-Cy-PEG may serve as a potential treatment in AD therapy.