Mild magnetic nanoparticle hyperthermia promotes the disaggregation and microglia-mediated clearance of beta-amyloid plaques

Dyne, Eric; Prakash, Praneetha Sundar; Li, Junfeng; Yu, Bing; Schmidt, Thorsten L.; Huang, Songping D.; Kim, Minho

doi:10.1016/j.nano.2021.102397

Cited by 11 publications

(9 citation statements)

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“…We recently showed that C20 microglia exposed to Aβ could readily phagocytose Aβ aggregates (Dyne et al, 2021). Our results in this study showed that Aβ-associated microglia transitioned into the activated state associated with a larger cell body, retracted minor processes, and observable crevices on the surface when compared to the control group.…”

Section: F I G U R Esupporting

confidence: 48%

“…Although the functional implication for this change in surface morphology remains to be further elucidated, we speculate that this may be associated with the activation of phagocytic pathways. We recently showed that C20 microglia exposed to Aβ could readily phagocytose Aβ aggregates (Dyne et al., 2021). Our results in this study showed that Aβ‐associated microglia transitioned into the activated state associated with a larger cell body, retracted minor processes, and observable crevices on the surface when compared to the control group.…”

Section: Discussionmentioning

confidence: 99%

“…Aβ plaque size was confirmed using dynamic light scattering analysis and transmission electron microscopy (TEM). Aβ fibrils were treated to C20 microglia at 1 μM for 24 h. This concentration was established by both performing a titration of β‐amyloid and analyzing C20 viability (Dyne et al., 2021) and by referencing the reported literature (Caldeira et al., 2017; Lue et al., 2001).…”

Section: Methodsmentioning

confidence: 99%

“…β-Amyloid (1 mg) was dissolved in 1,1,1,3,3,3-hexafluoropropan-2-ol ((CF 3 ) 2 CHOH) (HFIP) (1.5 ml) by brief sonication and vortex, and then stored overnight at ambient temperature (25 dynamic light scattering analysis and transmission electron microscopy (TEM). Aβ fibrils were treated to C20 microglia at 1 μM for 24 h. This concentration was established by both performing a titration of βamyloid and analyzing C20 viability (Dyne et al, 2021) and by referencing the reported literature (Caldeira et al, 2017;Lue et al, 2001).…”

Section: Preparation and Dosage Of Treatmentsmentioning

confidence: 99%

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Ultrastructural analysis of the morphological phenotypes of microglia associated with neuroinflammatory cues

Dyne

Cawood

Suzelis

et al. 2021

J of Comparative Neurology

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Microglia are the primary resident immune cells of the central nervous system that are responsible for the maintenance of brain homeostasis. There is a plethora of evidence to suggest that microglia display distinct phenotypes that are associated with the alteration of cell morphology under varying environmental cues. However, it has not been fully explored how the varying states of microglial activation are linked to the alteration of microglia morphology, especially in the microdomain. The objective of this study was to quantitatively characterize the ultrastructural morphology of human microglia under neuroinflammatory cues. To address this, a human cell line of microglia was stimulated by antiinflammatory (IL-4), proinflammatory (TNF-α), and Alzheimer's disease (AD)-associated cues (Aβ, Aβ + TNF-α). The resulting effects on microglia morphology associated with changes in microdomain were analyzed using a high-resolution scanning electron microscopy. Our findings demonstrated that microglial activation under proinflammatory and AD-cues were closely linked to changes not only in cell shape but also in cell surface topography and higher-order branching of processes. Furthermore, our results revealed that microglia under proinflammatory cues exhibited unique morphological features involving cell-to-cell contact and the formation of vesicle-like structures. Our study provides insight into the fine details of microglia morphology associated with varying status of microglial activation.

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Section: F I G U R Esupporting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Preparation and Dosage Of Treatmentsmentioning

confidence: 99%

See 2 more Smart Citations

Ultrastructural analysis of the morphological phenotypes of microglia associated with neuroinflammatory cues

Dyne

Cawood

Suzelis

et al. 2021

J of Comparative Neurology

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“…Previous studies indicated that MNPs can effectively improve the local temperature in the area extremely close to the MNPs (about 5 nm) through alternating the magnetic field, which reduces the penetration depth limit and damage to the neighboring tissues [ 111 , 112 ]. Therefore, it is a non-invasive strategy for clearing Aβ aggregates by using MNPs/AMF hyperthermia [ 113 ]. For instance, Loynachan et al used LPFFD-functionalized PEG-coated MNPs forthe remote magnetothermal disruption of Aβ aggregates under a high-frequency alternating magnetic field (AMF) ( Figure 7 C) [ 110 ].…”

Section: Nanomaterialsmentioning

confidence: 99%

Nanomaterials for Modulating the Aggregation of β-Amyloid Peptides

et al. 2021

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The aberrant aggregation of amyloid-β (Aβ) peptides in the brain has been recognized as the major hallmark of Alzheimer’s disease (AD). Thus, the inhibition and dissociation of Aβ aggregation are believed to be effective therapeutic strategiesforthe prevention and treatment of AD. When integrated with traditional agents and biomolecules, nanomaterials can overcome their intrinsic shortcomings and boost their efficiency via synergistic effects. This article provides an overview of recent efforts to utilize nanomaterials with superior properties to propose effective platforms for AD treatment. The underlying mechanismsthat are involved in modulating Aβ aggregation are discussed. The summary of nanomaterials-based modulation of Aβ aggregation may help researchers to understand the critical roles in therapeutic agents and provide new insight into the exploration of more promising anti-amyloid agents and tactics in AD theranostics.

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Nanomaterials as Microglia Modulators in the Treatment of Central Nervous System Disorders

Battaglini,

Marino,

Montorsi

et al. 2024

Adv Healthcare Materials

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Microglia play a pivotal role in the central nervous system (CNS) homeostasis, acting as housekeepers and defenders of the surrounding environment. These cells can elicit their functions by shifting into two main phenotypes: pro‐inflammatory classical phenotype, M1, and anti‐inflammatory alternative phenotype, M2. Despite their pivotal role in CNS homeostasis, microglia phenotypes can influence the development and progression of several CNS disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, ischemic stroke, traumatic brain injuries, and even brain cancer. It is thus clear as the possibility of modulating microglia activation has gained attention as a therapeutic tool against many CNS pathologies. Nanomaterials are an unprecedented tool for manipulating microglia responses, in particular to specifically target microglia and elicit an in situ immunomodulation activity. In this review we will focus our discussion on two main aspects: we will analyze the possibility of using nanomaterials to stimulate a pro‐inflammatory response of microglia against brain cancer and we will introduce nanostructures able to foster an anti‐inflammatory response for treating neurodegenerative disorders. The final aim is to stimulate the analysis of the development of new microglia nano‐immunomodulators, paving the way for innovative and effective therapeutic approaches for the treatment of CNS disorders.This article is protected by copyright. All rights reserved

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Mild magnetic nanoparticle hyperthermia promotes the disaggregation and microglia-mediated clearance of beta-amyloid plaques

Cited by 11 publications

References 50 publications

Ultrastructural analysis of the morphological phenotypes of microglia associated with neuroinflammatory cues

Ultrastructural analysis of the morphological phenotypes of microglia associated with neuroinflammatory cues

Nanomaterials for Modulating the Aggregation of β-Amyloid Peptides

Nanomaterials as Microglia Modulators in the Treatment of Central Nervous System Disorders

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