Acceleration and inhibition of amyloid-β fibril formation by peptide-conjugated fluorescent-maghemite nanoparticles

The formation of amyloid aggregates by association of peptides into ordered structures is hallmark of certain neurodegenerative disorders. Exploring the effect of specific nanoparticles on the formation of amyloid fibrils may contribute toward a mechanistic understanding of the aggregation processes, leading to design nanoparticles that modulate the formation of toxic amyloid plaques. Uniform maghemite (γ-Fe₂O₃) magnetic nanoparticles, containing fluorescein covalently encapsulated within (F-γ-Fe₂O₃)_, were prepared. These F-γ-Fe₂O₃ nanoparticles of 14.0 ± 4.0 nm were then coated with human serum albumin (HSA) via a precipitation process. Covalent conjugation of the spacer arm succinimidyl polyethylene glycol succinimidyl ester (NHS–PEG–NHS) to the F-γ-Fe₂O₃~HSA nanoparticles was then accomplished by interacting the primary amine groups of the HSA coating with excess NHS–PEG–NHS molecules. Covalent conjugation of the peptides amyloid-β 40 (Aβ₄₀) or Leu-Pro-Phe-Phe-Asp (LPFFD) onto the surface of the former fluorescent nanoparticles was then performed, by interacting the terminal activated NHS groups of the PEG derivatized F-γ-Fe₂O₃~HSA nanoparticles with primary amino groups of the peptides. Kinetics of the Aβ₄₀ fibrillation process in the absence and presence of varying concentrations of the Aβ₄₀ or LPFFD conjugated nanoparticles were also elucidated. The non-peptide conjugated fluorescent nanoparticles do not affect the Aβ₄₀ fibrillation process significantly. However, the Aβ₄₀-conjugated nanoparticles (F-γ-Fe₂O₃~HSA–PEG–Aβ₄₀) accelerate the fibrillation process while the LPFFD-conjugated nanoparticles (F-γ-Fe₂O₃~HSA–PEG–LPFFD) inhibit it. By applying MRI and fluorescence imaging techniques simultaneously these bioactive fluorescent magnetic iron oxide nanoparticles can be used as an efficient tool to study and control the Aβ₄₀ amyloid fibril formation process.