Targeted Magnetic Nanoparticles for Remote Magnetothermal Disruption of Amyloid-β Aggregates

Abstract

Remotely triggered hysteretic heat dissipation by magnetic nanoparticles (MNPs) selectively attached to targeted proteins can be used to break up self‐assembled aggregates. This magnetothermal approach is applied to the amyloid‐β (Aβ) protein, which forms dense, insoluble plaques characteristic of Alzheimer’s disease. Specific targeting of dilute MNPs to Aβ aggregates is confirmed via transmission electron microscopy (TEM) and is found to be consistent with a statistical model of MNP distribution on the Aβ substrates. MNP composition and size are selected to achieve efficient hysteretic power dissipation at physiologically safe alternating magnetic field (AMF) conditions. Dynamic light scattering, fluorescence spectroscopy, and TEM are used to characterize the morphology and size distribution of aggregates before and after exposure to AMF. A dramatic reduction in aggregate size from microns to tens of nanometers is observed, suggesting that exposure to an AMF effectively destabilizes Aβ deposits decorated with targeted MNPs. Experiments in primary hippocampal neuronal cultures indicate that the magnetothermal disruption of aggregates reduces Aβ cytotoxicity, which may enable future applications of this approach for studies of protein disaggregation in physiological environments.

Publication
Advanced healthcare materials
Colleen N Loynachan
Postdoc at EPFL (w/ Francesco Stellaci)
Gabriela Romero
Assistant Professor at University of Texas San Antonio
Michael G Christiansen
Postdoc at ETH Zurich (w/ Simone Schuerle)
Ritchie Chen
Postodoc at Stanford (w/ Karl Deisseroth)
Ulrich P Froriep
Project Director at Fraunhofer Institute
Polina Anikeeva
Polina Anikeeva
Associate Professor in Materials Science and Engineering
Associate Professor in Brain and Cognitive Sciences
Associate Director, Research Laboratory of Electronics

My goal is to combine the current knowledge of biology and nanoelectronics to develop materials and devices for minimally invasive treatments for neurological and neuromuscular diseases.

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