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

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