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Updated: Jun 13, 2026
Microglia as a Surrogate Biosensor to Determine Nanoparticle Neurotoxicity
Published on: October 25, 2016
Silica-based nanoparticle uptake and cellular response by primary microglia
Judy Choi1, Qingdong Zheng, Howard E Katz
1Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.
Background:
Silica nanoparticles (SiNPs) are being formulated for cellular imaging and for nonviral gene delivery in the central nervous system (CNS), but it is unclear what potential effects SiNPs can elicit once they enter the CNS. As the resident macrophages of the CNS, microglia are the cells most likely to respond to SiNP entry into the brain. Upon activation, they are capable of undergoing morphological and functional changes.
Objective:
We examined the effects of SiNP exposure using primary rat microglia.
Methods:
We observed microglial uptake of SiNPs using transmission electron and fluorescence confocal microscopy. Microglial functions, including phagocytosis, generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), expression of proinflammatory genes, and cytokine release, were measured after SiNP exposure at different concentrations.
Results:
Microglia are capable of avidly taking up SiNPs at all concentrations tested. These same concentrations did not elicit cytotoxicity or a change in phagocytic activity. SiNPs did increase the productions of both intracellular ROS and RNS. We also observed a significant decrease in tumor necrosis factor-alpha gene expression at all concentrations tested and a significant increase in COX-2 (cyclooxygenase-2) gene expression at the highest concentration of SiNPs. Analysis of cytokine release showed a detectable level of interleukin-1beta.
Conclusions:
This is the first study demonstrating the in vitro effects of SiNPs in primary microglia. Our findings suggest that very low levels of SiNPs are capable of altering microglial function. Increased ROS and RNS production, changes in proinflammatory genes, and cytokine release may not only adversely affect microglial function but also affect surrounding neurons.
Insights
Silica nanoparticles (SiNPs) alter key microglial functions in the central nervous system (CNS). Even at low doses, SiNPs increase reactive oxygen and nitrogen species, impacting brain cells.
Area of Science:
- Neuroscience
- Nanotechnology
- Immunology
Background:
- Silica nanoparticles (SiNPs) are explored for central nervous system (CNS) applications like imaging and gene delivery.
- Microglia, the CNS resident macrophages, are primary responders to foreign substances like SiNPs.
- Understanding SiNP effects on microglia is crucial due to their potential for morphological and functional changes.
Purpose of the Study:
- To investigate the in vitro effects of silica nanoparticles (SiNPs) on primary rat microglia.
- To assess SiNP uptake, cytotoxicity, and functional responses in microglia.
Main Methods:
- Microglial uptake of SiNPs was visualized using transmission electron and fluorescence confocal microscopy.
- Microglial functions including phagocytosis, reactive oxygen species (ROS) and reactive nitrogen species (RNS) production, proinflammatory gene expression, and cytokine release were measured.
- SiNP exposure was conducted at various concentrations.
Main Results:
- Primary microglia avidly internalized SiNPs across all tested concentrations without exhibiting cytotoxicity or altered phagocytosis.
- SiNP exposure led to increased intracellular ROS and RNS production.
- A significant decrease in tumor necrosis factor-alpha and an increase in COX-2 gene expression were observed, alongside detectable interleukin-1beta release.
Conclusions:
- This study provides the first in vitro evidence of SiNP effects on primary microglia.
- Low levels of SiNPs can modulate microglial function, including increased ROS/RNS production and altered gene expression.
- These SiNP-induced changes in microglia may negatively impact neuronal function within the CNS.
