ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
A nanomedicine transports a peptide caspase-3 inhibitor across the blood-brain barrier and provides neuroprotection.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 185 citations in OpenAlex.
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- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- Magnetic transferrin nanoparticles (MTNs) assay as a novel isolation approach for exosomal biomarkers in neurological diseases.Biomaterials research · 2023Article
- Polymer nanocarriers for targeted local delivery of agents in treating brain tumors.Nanotechnology · 2022Review
- Secondary Mitochondrial Dysfunction as a Cause of Neurodegenerative Dysfunction in Lysosomal Storage Diseases and an Overview of Potential Therapies.International journal of molecular sciences · 2022Review
- New Strategies for Stroke Therapy: Nanoencapsulated Neuroglobin.Pharmaceutics · 2022Review
- Nanoparticle delivery systems for substance use disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Review
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- Biological Implications of a Stroke Therapy Based in Neuroglobin Hyaluronate Nanoparticles. Neuroprotective Role and Molecular Bases.International journal of molecular sciences · 2021Article
- Physiological and Pathological Factors Affecting Drug Delivery to the Brain by Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- The Neurovascular Unit Dysfunction in Alzheimer's Disease.International journal of molecular sciences · 2021Review
- Therapeutic Strategies and Nano-Drug Delivery Applications in Management of Aging Alzheimer's Disease.Advances in experimental medicine and biology · 2021Review
- Nano drug delivery systems in upper gastrointestinal cancer therapy.Nano convergence · 2020Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Caspases play an important role as mediators of cell death in acute and chronic neurological disorders. Although peptide inhibitors of caspases provide neuroprotection, they have to be administered intracerebroventricularly because they cannot cross the blood-brain barrier (BBB). Herein, we present a nanocarrier system that can transfer chitosan nanospheres loaded with N-benzyloxycarbonyl-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethyl ketone (Z-DEVD-FMK), a relatively specific caspase-3 inhibitor, across BBB. Caspase-3 was chosen as a pharmacological target because of its central role in cell death. Polyethylene glycol-coated nanospheres were conjugated to an anti-mouse transferrin receptor monoclonal antibody (TfRMAb) that selectively recognizes the TfR type 1 on the cerebral vasculature. We demonstrate with intravital microscopy that this nanomedicine is rapidly transported across the BBB without being measurably taken up by liver and spleen. Pre- or post-treatment (2 h) with intravenously injected Z-DEVD-FMK-loaded nanospheres dose dependently decreased the infarct volume, neurological deficit, and ischemia-induced caspase-3 activity in mice subjected to 2 h of MCA occlusion and 24 h of reperfusion, suggesting that they released an amount of peptide sufficient to inhibit caspase activity. Similarly, nanospheres inhibited physiological caspase-3 activity during development in the neonatal mouse cerebellum on postnatal day 17 after closure of the BBB. Neither nanospheres functionalized with TfRMAb but not loaded with Z-DEVD-FMK nor nanospheres lacking TfRMAb but loaded with Z-DEVD-FMK had any effect on either paradigm, suggesting that inhibition of caspase activity and subsequent neuroprotection were due to efficient penetration of the peptide into brain. Thus, chitosan nanospheres open new and exciting opportunities for brain delivery of biologically active peptides that are useful for the treatment of CNS disorders.
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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.