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Effects of magnetic nanoparticle hyperthermia on the disruption of beta‐amyloid and microglia‐mediated inflammation
Author(s) -
Dyne Eric,
Li Junfeng,
Cawood Meghan,
Yu Bing,
Huang Songping,
Kim MinHo
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.044183
Subject(s) - microglia , inflammation , chemistry , amyloid beta , cell culture , biophysics , hyperthermia , peptide , magnetic nanoparticles , nanoparticle , microbiology and biotechnology , biochemistry , materials science , immunology , biology , nanotechnology , medicine , genetics
Background Insoluble and aggregated forms of beta‐amyloid peptides (Aβ) were shown to contribute to chronic inflammation in Alzheimer’s disease, in large part due to an impaired ability of microglial cells to clear Aβ when they form insoluble large aggregates. The objective of this study is to validate whether the application of mild magnetic nanoparticle (MNP) hyperthermia, which can generate heat on the surface of MNPs selectively attached to the Aβ aggregates to a remotely applied alternating magnetic field (AMF), is sufficient to disaggregate Aβ plaques and if then, can this alter the phagocytic and inflammatory responses of microglial cells towards the clearance of Aβ plaques. Methods Aggregated Aβ peptides were prepared by incubating beta‐amyloid 1‐42 peptides for 16 h, which resulted in 2‐10 um size of Aβ. Varying concentrations (1‐3 mg/mL) of MNPs (20 nm, paramagnetic nanoparticles) were added to the wells containing Aβ fibrils and incubated for 2 h, The samples were then treated with an AMF for 10 min duration at a field strength of 30 kA/m. The extent of Aβ disruption was assessed by using dynamic light scattering particle analysis and ultrastructure microscopy. The fragmented Aβ samples received with MNP/AMF were subsequently treated to the culture of human microglial cells (C20 cell line and HMC3 cell line (CRL‐3304™)), and changes in expression of pro‐ and anti‐inflammatory genes as well as phagocytic activity were quantified. Results The application of MNP/AMF for 10 min resulted in disaggregation of Aβ into smaller fragments, which was positively related to MNP concentration. The expression of pro‐inflammatory genes, IL‐1β and TNF‐α, in microglial cells were increased in the presence of large aggregate of Aβ plaques compared to an untreated control. However, the responses were significantly attenuated when cells were treated with Aβ plaques treated with MNP/AMF, which was associated with an increase in the uptake of Ab by microglia. Conclusions Our results demonstrate that a localized heating of magnetic nanoparticles localized around Aβ plaques is enough to disrupt the chemical bonds between beta‐amyloid plaques by destabilizing the aggregates, which could promote the functional activity of microglial cells towards clearance of beta‐amyloid debris, eliciting the attenuation of pro‐inflammatory signaling.