Copolymer Polydopamine Nanoparticles as Multifunctional Nanoinhibitors for Modulating β-Amyloid Aggregation

β-Amyloid (Aβ) aggregation is considered to be the pathological feature of Alzheimer’s disease (AD). Metal ions (such as Cu2+, Zn2+, Fe3+, etc.) can accelerate Aβ aggregation, leading to more severe neurotoxicity. Therefore, regulation of the self-assembly and metal-induced Aβ aggregation process is considered to be a promising method to alleviate the symptoms of AD. Herein, easy-to-synthesize, low-toxicity copolymer polydopamine nanoparticles (CPDA NPs), which were synthesized by the copolymerization of dopamine hydrochloride and poly(ethylene imine), were developed as neurotoxic metal chelates and inhibitors for the regulation of Aβ aggregation. CPDA NPs can not only effectively inhibit the self-assembly of Aβ monomers and oligomers but also disaggregate mature Aβ fibrils through noncovalent and covalent interactions. More importantly, because of the excellent metal-chelating properties of CPDA NPs, they can also effectively regulate metal (Cu2+, Fe3+, Mg2+, Zn2+, Al3+)-induced Aβ aggregation and reduce neurotoxicity caused by Aβ–metal complexes. Taken together, CPDA NPs can achieve effective regulation of multiple Aβ aggregation pathways through noncovalent and covalent interactions. This work is expected to provide an effective strategy for inhibiting and disaggregating Aβ fibrils or Aβ–metal complexes and offer insights for the development of an easy-to-synthesize, low-toxicity, and effective amyloid inhibitor.