ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
Targeting lipid nanoparticles to the blood-brain barrier to ameliorate acute ischemic stroke.
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Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50citing papers in PubMed
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50 citing papers in PubMed, 68 citations in OpenAlex.
- Preparation of targeted lipid nanoparticles for precision nucleic acid delivery.Nature protocols · 2026Review
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- Hypothalamic wars: the last nanodelivery.Reviews in endocrine & metabolic disorders · 2026Review
- Molecularly self-assembled nanoplatforms for targeted ROS-scavenging and neuroinflammation alleviation in acute ischemic stroke.Materials today. Bio · 2026Article
- Gene Therapy for Cardiovascular and Cerebrovascular Disease: Mechanisms, Translational Barriers, and the Road Ahead.Biomedicines · 2026Review
- Recent Developments in Lipid Nanoparticle-Mediated Delivery of Biotherapeutics and Gene Therapy Across the Blood-Brain Barrier.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Long noncoding RNA Nron and its functional motif modulate macrophage-mediated inflammatory response.Journal of advanced research · 2026Article
- Mechanisms and Therapeutic Targets of Ischemia-Reperfusion Injury in Stroke: A Narrative Review Focusing on Blood-Brain Barrier Dysfunction.Brain sciences · 2026Review
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- Chemokine Networks in Blood-Brain Barrier Regulation: Bidirectional Mechanisms, Clinical Translation, and Precision Therapeutic Prospects.Biomolecules · 2026Review
- Bioconjugates for improved delivery of oligonucleotide therapeutics to the central nervous system.Advanced drug delivery reviews · 2026Review
- Targeting DNA-LNPs to Endothelial Cells Improves Expression Magnitude, Duration, and Specificity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Endothelial ferroptosis in blood-brain barrier dysfunction and neuroinflammation: mechanisms and immune-vascular crosstalk.Frontiers in immunology · 2026Review
- Delivery of TCM Monomers Using Blood Cell Membrane Coated Biomimetic Nanoparticles to Target CVD.International journal of nanomedicine · 2026Review
- Spatiotemporally precise immune reprogramming: a new paradigm for next-generation neuroimmune therapy in ischemic stroke.Frontiers in neurology · 2026Review
- Decreased Anti-inflammatory IL-2 and IL-10 and Increased Mononuclear Cell Tissue Factor Correlate with Stroke Severity: Do Anti-inflammatory Cytokines Modulate Thrombosis?CNS & neurological disorders drug targets · 2026Article
- Intranasal Nano-Delivery Systems: Emerging Strategies for Central Nervous System Disease Therapeutics.International journal of nanomedicine · 2026Review
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Authors and funding
27 authors at 3 institutions in 2 countries.
Jia NongDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Patrick M GlassmanDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, Philadelphia, PA, USA.
Vladimir V ShuvaevDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Sahily Reyes-EstevesDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Helene C DescampsDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Raisa Y KiselevaDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Tyler E PappDivision of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Mohamad-Gabriel AlamehDivision of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ying K TamAcuitas Therapeutics, Vancouver, British Columbia V6T 1Z3, Canada.
Barbara L MuiAcuitas Therapeutics, Vancouver, British Columbia V6T 1Z3, Canada.
Serena Omo-LamaiDepartment of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA.
Marco E ZamoraDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Tea ShuvaevaDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Evguenia ArguiriDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Xijing GongDepartment of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA.
Taylor V BrysgelDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ai Wen TanDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ashley G WoolforkDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Aalim WeljieDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Christoph A ThaissDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jacob W MyersonDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Drew WeissmanDivision of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Scott E KasnerDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Hamideh ParhizDivision of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: hamideh.parhiz@pennmedicine.upenn.edu.
Vladimir R MuzykantovDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: muzykant@pennmedicine.upenn.edu.
Jacob S BrennerDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Pulmonary Allergy, and Critical Care, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: jacob.brenner@pennmedicine.upenn.edu.
Oscar A Marcos-ContrerasDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: oscarmar@pennmedicine.upenn.edu.
Translational Therapeutics (United States) · USUniversity of Pennsylvania · USAcuitas Therapeutics (Canada) · CA
Funding
PREDOCTORAL TRAINING PROGRAM IN PHARMACOLOGYT32GM008076 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BLENDY, JULIE A · 1985 to 2023
$10.8MVascular Targeting of Nanocarriers for RNAR01HL155106 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R, WEISSMAN, DREW · 2021 to 2024
$3.1MDual drug delivery to lung/blood interface in respiratory infections.R01HL157189 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2021 to 2024
$2.9MVascular delivery of nanocarriers by erythrocyresR01HL143806 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2018 to 2021
$2.8MmRNA-LNPs for ARDSR01HL164594 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Jacob Brenner, Hamideh Parhiz · 2023 to 2026
$2.7MControlling complement to unleash nanomedicine for acute critical illnessesR01HL160694 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI BRENNER, JACOB, MUZYKANTOV, VLADIMIR R · 2022 to 2025
$2.7MTargeting novel biotherapeutics to endotheliumR01HL128398 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2015 to 2018
$2.2MNanomedicine for ARDS: A new paradigm to target drugs to multiple cell types within alveolar capillariesR01HL153510 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI BRENNER, JACOB · 2020 to 2024
$2.0MTargeting the gatekeepers: Bolstering blood-brain barrier function using targeted nanomedicine in acute ischemic strokeR01NS131279 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI Oscar A. Marcos-Contreras · 2024 to 2026
$1.2MFcRn-enabling strategies for improved thrombolytic therapyR00HL153696 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI GLASSMAN, PATRICK MCKENNA · 2022 to 2024
$747kNanonscale drug carriers for the treatment of acute respiratory distress syndromeK08HL138269 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI BRENNER, JACOB · 2017 to 2021
$746kNext-generation nanomedicine for acute ischemic strokeR41NS130812 · NINDS · NANOMUSE, LLC · PI BRENNER, JACOB · 2023 to 2025
$652kNHLBI NIH HHS F31 HL154662NHLBI NIH HHS K08 HL138269NHLBI NIH HHS K99 HL153696NHLBI NIH HHS R00 HL153696NHLBI NIH HHS R01 HL128398NHLBI NIH HHS R01 HL143806NHLBI NIH HHS R01 HL153510NHLBI NIH HHS R01 HL155106NHLBI NIH HHS R01 HL157189NHLBI NIH HHS R01 HL160694NHLBI NIH HHS R01 HL164594NIAID NIH HHS R21 AI166778NIGMS NIH HHS T32 GM008076NINDS NIH HHS L70 NS134081NINDS NIH HHS R01 NS131279NINDS NIH HHS R41 NS130812
Abstract
Effective delivery of mRNA or small molecule drugs to the brain is a significant challenge in developing treatment for acute ischemic stroke (AIS). To address the problem, we have developed targeted nanomedicine to increase drug concentrations in endothelial cells of the blood-brain barrier (BBB) of the injured brain. Inflammation during ischemic stroke causes continuous neuronal death and an increase in the infarct volume. To enable targeted delivery to the inflamed BBB, we conjugated lipid nanocarriers (NCs) with antibodies that bind cell adhesion molecules expressed at the BBB. In the transient middle cerebral artery occlusion mouse model, NCs targeted to vascular cellular adhesion molecule-1 (VCAM) achieved the highest level of brain delivery, nearly two orders of magnitude higher than untargeted ones. VCAM-targeted lipid nanoparticles with luciferase-encoding mRNA and Cre-recombinase showed selective expression in the ischemic brain. Anti-inflammatory drugs administered intravenously after ischemic stroke reduced cerebral infarct volume by 62% (interleukin-10 mRNA) or 35% (dexamethasone) only when they were encapsulated in VCAM-targeted NCs. Thus, VCAM-targeted lipid NCs represent a new platform for strongly concentrating drugs within the compromised BBB of penumbra, thereby ameliorating AIS.
Indexed as
Blood-Brain BarrierDisease Models, AnimalIschemic StrokeLiposomesNanoparticlesVascular Cell Adhesion Molecule-1AnimalsDrug Delivery SystemsHumansInfarction, Middle Cerebral ArteryLipidsMiceLipid NanoparticlesLipidsLiposomesVascular Cell Adhesion Molecule-1drug deliverydrug targetingischemic strokelipid nanoparticlesneurovascular inflammation
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