ArticleProceedings of the National Academy of Sciences of the United States of America2020
Targeting nanoparticles to the brain by exploiting the blood-brain barrier impermeability to selectively label the brain endothelium.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 128 citations in OpenAlex.
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- Nanoparticles Navigating the Blood-Brain Barrier for Neurodegenerative Therapy.International journal of nanomedicine · 2026Review
- Revolutionizing Therapeutic Approaches Against Pathophysiology of Alzheimer's Disease: A Therapeutic Review.Current aging science · 2026Review
- Targeted Nanoparticles for Drug Delivery Across the Blood-Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review.Molecular neurobiology · 2025Review
- Recent advances in biomimetic nanodelivery systems for the treatment of depression.Materials today. Bio · 2025Review
- Harnessing stimuli-responsive biomaterials for advanced biomedical applications.Exploration (Beijing, China) · 2025Review
- Unraveling Neurological Drug Delivery: Polymeric Nanocarriers for Enhanced Blood-Brain Barrier Penetration.Current drug targets · 2025Review
- Nanoparticles: a new frontier in neurodegenerative disease therapy.Frontiers in medical technology · 2025Review
- Nanoparticles in CNS Therapeutics: Pioneering Drug Delivery Advancements.Current pharmaceutical design · 2025Review
- Nanoparticle targeting strategies for traumatic brain injury.Journal of neural engineering · 2024Review
- Metformin carbon dots enhance neurogenesis and neuroprotection in Alzheimer's disease: A potential nanomedicine approach.Materials today. Bio · 2024Article
- Status Quo in the Liposome-Based Therapeutic Strategies Against Glioblastoma: "Targeting the Tumor and Tumor Microenvironment".International journal of molecular sciences · 2024Review
- Nanocarriers for targeted drug delivery in the vascular system: focus on endothelium.Journal of nanobiotechnology · 2024Review
- Oral administration of crocin-loaded solid lipid nanoparticles inhibits neuroinflammation in a rat model of epileptic seizures by activating SIRT1 expression.Research in pharmaceutical sciences · 2024Article
- Exploring the potential of cell-derived vesicles for transient delivery of gene editing payloads.Advanced drug delivery reviews · 2024Review
- Emerging Perspectives on Prime Editor Delivery to the Brain.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Impact of protein coronas on nanoparticle interactions with tissues and targeted delivery.Current opinion in biotechnology · 2024Review
- Endothelial cellular senescence and tau accumulation: An interplay full of opportunities?Ibrain · 2024Article
- Navigating the nano-bio immune interface: advancements and challenges in CNS nanotherapeutics.Frontiers in immunology · 2024Review
- Identifying molecular tags selectively retained on the surface of brain endothelial cells to generate artificial targets for therapy delivery.Fluids and barriers of the CNS · 2023Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Current strategies to direct therapy-loaded nanoparticles to the brain rely on functionalizing nanoparticles with ligands which bind target proteins associated with the blood-brain barrier (BBB). However, such strategies have significant brain-specificity limitations, as target proteins are not exclusively expressed at the brain microvasculature. Therefore, novel strategies which exploit alternative characteristics of the BBB are required to overcome nonspecific nanoparticle targeting to the periphery, thereby increasing drug efficacy and reducing detrimental peripheral side effects. Here, we present a simple, yet counterintuitive, brain-targeting strategy which exploits the higher impermeability of the BBB to selectively label the brain endothelium. This is achieved by harnessing the lower endocytic rate of brain endothelial cells (a key feature of the high BBB impermeability) to promote selective retention of free, unconjugated protein-binding ligands on the surface of brain endothelial cells compared to peripheral endothelial cells. Nanoparticles capable of efficiently binding to the displayed ligands (i.e., labeled endothelium) are consequently targeted specifically to the brain microvasculature with minimal "off-target" accumulation in peripheral organs. This approach therefore revolutionizes brain-targeting strategies by implementing a two-step targeting method which exploits the physiology of the BBB to generate the required brain specificity for nanoparticle delivery, paving the way to overcome targeting limitations and achieve clinical translation of neurological therapies. In addition, this work demonstrates that protein targets for brain delivery may be identified based not on differential tissue expression, but on differential endocytic rates between the brain and periphery.
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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.