A Peptide-Polyphenol Coated Polypyrrole Nanoparticle for Synergetic Attenuation of Aggregation and Cytotoxicity of Amyloid- Fibrils

Amyloid-beta (A beta) pathway is positioned as the center for Alzheimer's disease (AD) pathophysiology. Viable drugs targeting A beta pathway are developed with promising outcomes. Meanwhile, most current approaches are focused on the inhibition of A beta fibrillization or elimination of A beta plaques by immunotherapeutic strategies. Here, near-infrared (NIR) photothermal polypyrrole nanoparticles coated with peptide-polyphenol are developed to both inhibit the A beta fibrillization and disaggregate A beta fibrils synergistically. A beta fibrillization is obviously inhibited after being treated with the photothermal polypyrrole nanoparticles. Besides inhibition of A beta fibrillization, the amount of A beta fibrils is gradually reduced with time by 38.0% when co-incubated with polypyrrole nanoparticles, indicating desired disaggregation capability against A beta fibrils. In addition, faster and more disaggregation of A beta fibrils is observed when irradiation by NIR light. Meanwhile, cellular studies also verified that this nanoparticle is able to effectively reduce the cytotoxicity of A beta fibrils toward PC12 cells through disaggregating toxic A beta aggregates and maintaining integral membrane structure. Hence, this peptide-polyphenol-coated NIR photothermal polypyrrole nanoparticle provides a new perspective for the inhibition of A beta fibrillization and disaggregation of A beta fibrils, which can serve as a promising approach for anti-amyloidosis.