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.