Microglia nanomaterials

Glioblastoma multiforme (GBM) is the most aggressive brain cancer, characterized by a rapid and drug-resistant progression. GBM "builds" around its primary core a genetically heterogeneous tumor-microenvironment (TME), recruiting surrounding healthy brain cells by releasing various intercellular signals. Glioma-associated microglia (GAM) represent the largest population of collaborating cells, which, in the TME, usually exhibit the anti-inflammatory M2 phenotype, thus promoting an immunosuppressing environment that helps tumor growth...

Disordered reactive oxygen/nitrogen species are a common occurrence in various diseases, which usually cause cellular oxidative damage and inflammation. Despite the wide range of applications for biomimetic nanoparticles with antioxidant or anti-inflammatory properties, designs that seamlessly integrate these two abilities with a synergistic effect in a simple manner are seldom reported. In this study, we developed a novel PEI-Mn composite nanoparticle (PM NP) using a chelation method, and the curcumin was loaded onto PM NPs via metal-phenol coordination to form PEI-Mn@curcumin nanoparticles (PMC NPs)...

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...

Fungal nanochitin can assist the transition from the linear fossil-based economy to a circular biobased economy given its environmental benefits over conventional crustacean-nanochitin. Its real-world implementation requires carefully assessing its toxicity so that unwanted human health and environmental issues are avoided. Accordingly, the cytotoxicity and inflammatory effects of chitin nanofibrils (ChNFs) from white mushroom is assessed. ChNFs are few nanometers in diameter, with a 75.8% N -acetylation degree, a crystallinity of 59...

Central nervous system (CNS) glia, including astrocytes, microglia, and oligodendrocytes, play prominent roles in traumatic injury and degenerative disorders. Due to their importance, active pharmaceutical ingredients (APIs) are being developed to modulate CNS glia in order to improve outcomes in traumatic injury and disease. While many of these APIs show promise in vitro, the majority of APIs that are systemically delivered show little penetration through the blood-brain barrier (BBB) or blood-spinal cord barrier (BSCB) and into the CNS, rendering them ineffective...

Silver nanoparticles (AgNPs) have durable and remarkable antimicrobial effects on pathogenic microorganisms, such as bacteria and fungi, in dental plaques. As such, they are widely added to dental restoration materials, including composite resins, denture bases, adhesives, and implants, to solve the problems of denture stomatitis, peri-implant inflammation, and oral infection caused by the long-term use of these dental restoration materials. However, AgNPs can be absorbed into the blood circulatory system through the nasal/oral mucosa, lungs, gastrointestinal tract, skin, and other pathways and then distributed into the lungs, kidneys, liver, spleen, and testes, thereby causing toxic injury to these tissues and organs...

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of old age. Accumulation of β-amyloid peptide (Aβ) and mitochondrial dysfunction results in chronic microglial activation, which enhances neuroinflammation and promotes neurodegeneration. Microglia are resident macrophages of the brain and spinal cord which play an important role in maintaining brain homeostasis through a variety of phenotypes, including the pro-inflammatory phenotype and anti-inflammatory phenotypes. However, persistently activated microglial cells generate reactive species and neurotoxic mediators...

Organotypic slice culture models surpass conventional in vitro methods in many aspects. They retain all tissue-resident cell types and tissue hierarchy. For studying multifactorial neurodegenerative diseases such as tauopathies, it is crucial to maintain cellular crosstalk in an accessible model system. Organotypic slice cultures from postnatal tissue are an established research tool, but adult tissue-originating systems are missing, yet necessary, as young tissue-originating systems cannot fully model adult or senescent brains...

Inflammatory responses, manifested in excessive oxidative stress and microglia overactivation, together with metal ion-triggered amyloid-beta (Aβ) deposition, are critical hallmarks of Alzheimer's disease (AD). The intricate pathogenesis causes severe impairment of neurons, which, in turn, exacerbates Aβ aggregation and facilitates AD progression. Herein, multifunctional melanin-like metal ion chelators and neuroinflammation regulators (named PDA@K) were constructed for targeted treatment of AD...

Occupational injuries and toxicant exposures lead to the development of neuroinflammation by activating distinct mechanistic signaling cascades that ultimately culminate in the disruption of neuronal function leading to neurological and neurodegenerative disorders. The entry of toxicants into the brain causes the subsequent activation of glial cells, a response known as 'reactive gliosis'. Reactive glial cells secrete a wide variety of signaling molecules in response to neuronal perturbations and thus play a crucial role in the progression and regulation of central nervous system (CNS) injury...

Neural interfaces provide a window for bio-signal modulation and recording with the assistance of neural microelectrodes. However, shrinking the size of electrodes results in high electrochemical impedance and low capacitance, thus limiting the stimulation/recording efficiency. In order to achieve critical stability and low power consumption, here, nanocone-shaped platinum (Pt) with an extensive surface area is proposed as an adhesive layer on a bare Pt substrate, followed by the deposition of a thin layer of iridium oxide (IrOx ) to fabricate high-performance nanocone-array-based Pt-IrOx neural microelectrodes (200 μm in diameter)...

Spinal cord regeneration after a spinal cord injury (SCI) remains a difficult challenge due to the complicated inflammatory microenvironment and neuronal damage at the injury sites. In this study, retinoic acid (RA) and curcumin (Cur) were co-loaded with bovine serum albumin (BSA) self-assembly to obtain RA@BSA@Cur nanoparticles (NPs) for SCI treatment. Cur, as an antioxidant drug, facilitated reactive oxygen species (ROS) scavenging, and decreased the amount of inflammatory factors secreted by macrophages, while RA could enhance neurite extensions and neural differentiation...

Engineered silver nanoparticles (AgNPs), including silver silicate nanoparticles (Ag-SiO2 NPs), are used in a wide variety of medical and consumer applications. Inhaled AgNPs have been found to translocate to the olfactory bulb (OB) after inhalation and intranasal instillation. However, the biological effects of Ag-SiO2 NPs and their potential nose-to-brain transport have not been evaluated. The present study assessed whether inhaled Ag-SiO2 NPs can elicit microglial activation in the OB. Adult Sprague-Dawley rats inhaled aerosolized Ag-SiO2 NPs at a concentration of 1 mg/ml for 6 hours...

Parkinson's disease (PD) is an age-related neurodegenerative disease, and the removal of senescent cells has been proved to be beneficial for improving age-associated pathologies in neurodegeneration disease. In this study, chiral gold nanoparticles (NPs) with different helical directions were synthesized to selectively induce the apoptosis of senescent cells under light illumination. By modifying anti-B2MG and anti-DCR2 antibodies, senescent microglia cells could be cleared by chiral NPs without damaging the activities of normal cells under illumination...

Ischemic stroke activates toll-like receptor 4 (TLR4) signaling, resulting in proinflammatory polarization of microglia and secondary neuronal damage. Herein, we report a novel lipid-nanoparticle (LNP)-mediated knockdown of TLR4 in microglia and amelioration of neuroinflammation in a mouse model of transient middle cerebral artery occlusion (tMCAO). siRNA against TLR4 (siTLR4) complexed to the novel LNP (siTLR4/DoGo310), which was based on a dioleoyl-conjugated short peptidomimetic (denote DoGo310), was readily internalized by the oxygen-glucose-deprived (OGD) mouse primary microglia, knocked-down TLR4, and polarized the cell to the anti-inflammatory phenotype in vitro...

BACKGROUND: Along with the wild applications of nitrogen-doped graphene quantum dots (N-GQDs) in the fields of biomedicine and neuroscience, their increasing exposure to the public and potential biosafety problem has gained more and more attention. Unfortunately, the understanding of adverse effects of N-GQDs in the central nervous system (CNS), considered as an important target of nanomaterials, is still limited. RESULTS: After we found that N-GQDs caused cell death, neuroinflammation and microglial activation in the hippocampus of mice through the ferroptosis pathway, microglia was used to assess the molecular mechanisms of N-GQDs inducing ferroptosis because it could be the primary target damaged by N-GQDs in the CNS...

A unique morphological Sesamum radiatum oil/polyvinylpyrrolidone/gold polymeric bionanocomposite film was synthesized using the S. radiatum oil dispersed in a polymeric polyvinylpyrrolidone (PVP) matrix and decorated with gold nanoparticles (AuNPs). The chemical and physical characteristics as well as the thermal stability of the synthesized bionanocomposite film were investigated using various spectroscopic and microscopic techniques. The microscopic analysis confirmed well dispersed AuNPs in the PVP- S. radiatum oil matrix with particle size of 100 nm...

Functional nanomaterials such as iron oxide nanoparticles have been extensively explored for the diagnosis and treatment of central nervous system diseases. However, an insufficient understanding of the comprehensive nanomaterial-biological interactions in the brain hinders the nanomaterials from meeting the medical requirements for translational research. Here, FDA-approved ferumoxytol, an iron oxide nanoparticle, is chosen as the model nanomaterial for a systematic study of the dynamic interactions between ferumoxytol and immune cells, including microglia and macrophages, in the brain tumors...

Reactive microgliosis is a pathological hallmark that accompanies neuronal demise in many neurodegenerative diseases, ranging from acute brain/spinal cord injuries to chronic diseases, such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and age-related dementia. One strategy to assess and monitor microgliosis is to use positron emission tomography (PET) by exploiting radioligands selective for the 18 kDa translocator protein (TSPO) which is highly upregulated in the brain in pathological conditions...

Gold nanoparticles hold a great promise for both clinical and preclinical applications. The major factors impeding such applications are toxicity of new nanomaterials including e.g., pro-apoptotic activities or inflammatory effects, but also their potential to accumulate in the body or inadequate absorption, distribution, metabolism and excretion (ADME) profiles. Since such adverse effects depend on the size, form and coating of nanomaterials, the search for new, less toxic nanomaterials with low tendency to accumulate is highly active domain of research...