ArticlePharmaceutics2022
Brain Delivery of IGF1R5, a Single-Domain Antibody Targeting Insulin-like Growth Factor-1 Receptor.
Article in Pharmaceutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- Article
- Antibody-Based Biologics for CNS Disorders.Antibodies (Basel, Switzerland) · 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
- Engineering a dimeric single-domain antibody for improved detection and neutralization of amyloid-β oligomers.Communications biology · 2026Article
- Bioconjugates for improved delivery of oligonucleotide therapeutics to the central nervous system.Advanced drug delivery reviews · 2026Review
- Bridging the blood-brain barrier: strategies to improve delivery of biologics to tumors in the brain.Fluids and barriers of the CNS · 2026Review
- Magnetic Nanoparticles as a Theranostic Platform in Brain Tumor Treatment: Surmounting the Bench-to-Bedside Barriers.International journal of nanomedicine · 2026Review
- The Design Strategies and Applications of Engineered Nanoparticles for Traumatic Brain Injury.International journal of nanomedicine · 2026Review
- Article
- Bispecific self-assembled peptides as supra-growth factors for preventing endotheliopathy and improving survival of traumatic brain injury in mice.Journal of nanobiotechnology · 2025Article
- Highly conserved brain vascular receptor ALPL mediates transport of engineered AAV vectors across the blood-brain barrier.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Beyond the Walls of Troy: A Scoping Review on Pharmacological Strategies to Enhance Drug Delivery Across the Blood-Brain Barrier and Blood-Tumor Barrier.International journal of molecular sciences · 2025Article
- Crossing the Blood-Brain Barrier: Innovations in Receptor- and Transporter-Mediated Transcytosis Strategies.Pharmaceutics · 2025Review
- Advances in brain-targeted delivery strategies and natural product-mediated enhancement of blood-brain barrier permeability.Journal of nanobiotechnology · 2025Review
- In vivo brain delivery of BBB-enabled iduronate 2-sulfatase in rats.Fluids and barriers of the CNS · 2025Article
- Blood-Brain Barrier Conquest in Glioblastoma Nanomedicine: Strategies, Clinical Advances, and Emerging Challenges.Cancers · 2024Review
- Growth Factors and Their Application in the Therapy of Hereditary Neurodegenerative Diseases.Biomedicines · 2024Review
- Emerging Perspectives on Prime Editor Delivery to the Brain.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Receptor-mediated transcytosis for brain delivery of therapeutics: receptor classes and criteria.Frontiers in drug delivery · 2024Review
- Recombinant Antibody Fragments for Neurological Disorders: An Update.Current neuropharmacology · 2024Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ability of drugs and therapeutic antibodies to reach central nervous system (CNS) targets is greatly diminished by the blood-brain barrier (BBB). Receptor-mediated transcytosis (RMT), which is responsible for the transport of natural protein ligands across the BBB, was identified as a way to increase drug delivery to the brain. In this study, we characterized IGF1R5, which is a single-domain antibody (sdAb) that binds to insulin-like growth factor-1 receptor (IGF1R) at the BBB, as a ligand that triggers RMT and could deliver cargo molecules that otherwise do not cross the BBB. Surface plasmon resonance binding analyses demonstrated the species cross-reactivity of IGF1R5 toward IGF1R from multiple species. To overcome the short serum half-life of sdAbs, we fused IGF1R5 to the human (hFc) or mouse Fc domain (mFc). IGF1R5 in both N- and C-terminal mFc fusion showed enhanced transmigration across a rat BBB model (SV-ARBEC) in vitro. Increased levels of hFc-IGF1R5 in the cerebrospinal fluid and vessel-depleted brain parenchyma fractions further confirmed the ability of IGF1R5 to cross the BBB in vivo. We next tested whether this carrier was able to ferry a pharmacologically active payload across the BBB by measuring the hypothermic and analgesic properties of neurotensin and galanin, respectively. The fusion of IGF1R5-hFc to neurotensin induced a dose-dependent reduction in the core temperature. The reversal of hyperalgesia by galanin that was chemically linked to IGF1R5-mFc was demonstrated using the Hargreaves model of inflammatory pain. Taken together, our results provided a proof of concept that appropriate antibodies, such as IGF1R5 against IGF1R, are suitable as RMT carriers for the delivery of therapeutic cargos for CNS applications.
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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.