ArticleMolecules (Basel, Switzerland)2018
Preferential and Increased Uptake of Hydroxyl-Terminated PAMAM Dendrimers by Activated Microglia in Rabbit Brain Mixed Glial Culture.
Article in Molecules (Basel, Switzerland), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- Article
- Advancing brain immunotherapy through functional nanomaterials.Drug delivery and translational research · 2026Review
- A radiolabeled dendrimer non-invasively identifies and tracks innate immune cell activation in a mouse model of experimental autoimmune encephalomyelitis.Nature communications · 2026Article
- Advancements in Neonatal Brain Injury Treatment: Nanomedicine-Based Strategies.International journal of nanomedicine · 2026Review
- Inhibition of microglial glutaminase alleviates chronic stress-induced neurobehavioral and cognitive deficits.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Mixed-Layered Glycodendrimer Probe for Imaging Inflammation at Surgical Site Infections.ACS sensors · 2025Article
- Biomaterial strategies for regulating the neuroinflammatory response.Materials advances · 2024Review
- Dendrimer nanotherapy targeting of glial dysfunction improves inflammation and neurobehavioral phenotype in adult female Mecp2-heterozygous mouse model of Rett syndrome.Journal of neurochemistry · 2024Article
- Development and Initial Assessment of [Molecular imaging and biology · 2023Article
- Clinical Radiosynthesis and Translation of [ACS chemical neuroscience · 2023Article
- Galactosylated hydroxyl-polyamidoamine dendrimer targets hepatocytes and improves therapeutic outcomes in a severe model of acetaminophen poisoning-induced liver failure.Bioengineering & translational medicine · 2023Article
- Dendrimers and Derivatives as Multifunctional Nanotherapeutics for Alzheimer's Disease.Pharmaceutics · 2023Review
- Targeted Microglial Attenuation through Dendrimer-Drug Conjugates Improves Glaucoma Neuroprotection.Biomacromolecules · 2023Article
- Dendrimer-2PMPA selectively blocks upregulated microglial GCPII activity and improves cognition in a mouse model of multiple sclerosis.Nanotheranostics · 2022Article
- Mechanisms Involved in Microglial-Interceded Alzheimer's Disease and Nanocarrier-Based Treatment Approaches.Journal of personalized medicine · 2021Review
- Targeted drug delivery for maternal and perinatal health: Challenges and opportunities.Advanced drug delivery reviews · 2021Review
- Dendrimer-Triamcinolone Acetonide Reduces Neuroinflammation, Pathological Angiogenesis, and Neuroretinal Dysfunction in Ischemic Retinopathy.Advanced therapeutics · 2021Article
- Optimization and computational studies evaluating molecular dynamics of EDA cored polymeric dendrimer.Scientific reports · 2020Article
- Governing Transport Principles for Nanotherapeutic Application in the Brain.Current opinion in chemical engineering · 2020Article
- Microglia-targeting nanotherapeutics for neurodegenerative diseases.APL bioengineering · 2020Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Polyamidoamine (PAMAM) dendrimers are multifunctional nanoparticles with tunable physicochemical features, making them promising candidates for targeted drug delivery in the central nervous system (CNS). Systemically administered dendrimers have been shown to localize in activated glial cells, which mediate neuroinflammation in the CNS. These dendrimers delivered drugs specifically to activated microglia, producing significant neurological improvements in multiple brain injury models, including in a neonatal rabbit model of cerebral palsy. To gain further insight into the mechanism of dendrimer cell uptake, we utilized an in vitro model of primary glial cells isolated from newborn rabbits to assess the differences in hydroxyl-terminated generation 4 PAMAM dendrimer (D4-OH) uptake by activated and non-activated glial cells. We used fluorescently-labelled D4-OH (D-Cy5) as a tool for investigating the mechanism of dendrimer uptake. D4-OH PAMAM dendrimer uptake was determined by fluorescence quantification using confocal microscopy and flow cytometry. Our results indicate that although microglial cells in the mixed cell population demonstrate early uptake of dendrimers in this in vitro system, activated microglia take up more dendrimer compared to resting microglia. Astrocytes showed delayed and limited uptake. We also illustrated the differences in mechanism of uptake between resting and activated microglia using different pathway inhibitors. Both resting and activated microglia primarily employed endocytotic pathways, which are enhanced in activated microglial cells. Additionally, we demonstrated that hydroxyl terminated dendrimers are taken up by primary microglia using other mechanisms including pinocytosis, caveolae, and aquaporin channels for dendrimer uptake.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.