Interplay between Amyloid Fibrillation Delay and Degradation by Magnetic Zinc-Doped Ferrite Nanoparticles.

Abstract

Amyloidosis, the aggregation of naturally soluble proteins into fibrils, is the main pathological hallmark of central nervous system (CNS) disorders, and new therapeutic approaches can be introduced through nanotechnology. Herein, magnetic nanoparticles (MNPs) are proposed to combat amyloidosis and act as CNS theranostic (therapy and diagnosis) candidates through magnetomechanical forces that can be induced under a low-frequency magnetic field. In that vein, a modified one-step microwave-assisted polyol process has been employed to synthesize hybrid organic/inorganic zinc ferrite (ZnxFe3-xO4) MNPs with different levels of zinc doping (0.30 < x < 0.6) derived from the utilized polyol. The lowest doped (x = 0.30) MNPs exhibited high magnetization (127 emu/g), high T2 imaging ability (r2 = 432 mM-1 s-1), and relatively small hydrodynamic size (180 nm), decisive characteristics to further evaluate their CNS theranostic potential. Their effect on the fibrillation/degradation was monitored in two model proteins, insulin and albumin, in the presence/absence of variant external magnetic fields (static, rotating, or alternating) via Thioflavin T (ThT) fluorescence assay and optical fluorescence microscopy. The MNPs were injected either in oligomer solution where significant fibrillation delay was observed, boosted by zinc ionic leaching of MNPs, or in already formed amyloid plaques where up to 86% amyloid degradation was recorded in the presence of magnetic fields, unveiling magnetomechanical antifibrillation properties. The alternating magnetic field (4 Hz) allows the bouncing of the MNPs into the amyloid net driven by the magnetic forces, and thus is featured as the preferred "dancing mode", which strengthens the degrading efficacy of MNPs.