ArticleACS nano2014
Dendrimer brain uptake and targeted therapy for brain injury in a large animal model of hypothermic circulatory arrest.
Article in ACS nano, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 152 citations in OpenAlex.
- Advances in Dendrimer-Based Anti-Infective Systems: In Vivo Insights and Perspectives.Pharmaceutics · 2026Review
- A radiolabeled dendrimer non-invasively identifies and tracks innate immune cell activation in a mouse model of experimental autoimmune encephalomyelitis.Nature communications · 2026Article
- Engineering pH-Responsive Dendrimer-STAT3 Inhibitor Conjugates for Intracellular Delivery.Biomacromolecules · 2026Article
- Host-directed nanotherapy for the treatment and imaging of tuberculous meningitis.Theranostics · 2026Article
- Inhibition of microglial glutaminase alleviates chronic stress-induced neurobehavioral and cognitive deficits.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Layer-Specific Colocalization of Microglia with Amyloid Plaques in the Middle Temporal Gyrus Predicts Cognitive Decline in Alzheimer's Disease.Aging and disease · 2025Article
- Efficient Intracellular Delivery of CRISPR-Cas9 Ribonucleoproteins Using Dendrimer Nanoparticles for Robust Genomic Editing.Nano today · 2025Article
- Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Exploring the Potential of Non-Viral Nanocarriers for Improving Blood-Brain Barrier Permeability to Enhance the Treatment of Brain Diseases.International journal of nanomedicine · 2025Review
- Novel Drug Delivery Systems: An Important Direction for Drug Innovation Research and Development.Pharmaceutics · 2024Review
- Selective targeting and modulation of plaque associated microglia via systemic hydroxyl dendrimer administration in an Alzheimer's disease mouse model.Alzheimer's research & therapy · 2024Article
- Mitochondria-Targeted Antioxidant Therapeutics for Traumatic Brain Injury.Antioxidants (Basel, Switzerland) · 2024Review
- Development and Initial Assessment of [Molecular imaging and biology · 2023Article
- Adverse Effects of Non-Metallic Nanoparticles in the Central Nervous System.Materials (Basel, Switzerland) · 2023Review
- Microglial-Targeted nSMase2 Inhibitor Fails to Reduce Tau Propagation in PS19 Mice.Pharmaceutics · 2023Article
- Clinical Radiosynthesis and Translation of [ACS chemical neuroscience · 2023Article
- Dendrimer-enabled targeted delivery attenuates glutamate excitotoxicity and improves motor function in a rabbit model of cerebral palsy.Journal of controlled release : official journal of the Controlled Release Society · 2023Article
- Nanoparticle-based targeting of microglia improves the neural regeneration enhancing effects of immunosuppression in the zebrafish retina.Communications biology · 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
19 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer-drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems.
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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.