Targeted magnetic nanoparticles for remote manipulation of protein aggregation

Abstract

Local heat delivered by magnetic nanoparticles (MNPs) selectively attached to their target proteins can be used to manipulate and break up toxic or obstructive aggregates. We applied this magnetic hyperthermia treatment to the amyloid beta (A[beta]) peptide, which unnaturally folds and self-assembles forming amyloid fibrils and insoluble plaques characteristic of amyloidgenic diseases such as Alzheimer's disease. We demonstrate remote disaggregation of A[beta] aggregates using heat dissipated by ferrite MNPs in the presence of an alternating magnetic field (AMF). Specific targeting was achieved by MNP functionalization with a targeting peptide sequence that binds a hydrophobic domain of A[beta]. AMF parameters and MNP composition and size were tailored to maximize hysteretic power losses. Transmission electron microscopy image analysis and thioflavin T fluorescence spectroscopy were used to characterize the morphology and size distribution of aggregates before and after AMF stimulus. We found that the AMF stimulus is effective at destabilizing A[beta] deposits and causing a reduction in aggregate size. This targeting scheme has potential as a therapy for amyloidosis and as a minimally invasive tool for analyzing and controlling protein aggregation.