Targeted magnetic nanoparticles for remote manipulation of protein aggregation

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.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Materials Science and Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2014

Author dc:creator

• Loynachan, Colleen

Advisor dc:contributor.advisor

• Polina Anikeeva.

• Materials Science and Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/98002

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/98002