Academic Journal
ICAM-1 targeting of nanocarriers in a human blood-brain-barrier-on-a-chip complements in vivo brain delivery observations.
| Τίτλος: | ICAM-1 targeting of nanocarriers in a human blood-brain-barrier-on-a-chip complements in vivo brain delivery observations. |
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| Συγγραφείς: | Vigo M; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.; Biomedicine Doctorate Program, University of Barcelona (UB), Barcelona, Spain., Palma-Florez S; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.; Biomedicine Doctorate Program, University of Barcelona (UB), Barcelona, Spain., Grimalt-Mirada R; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain., Placci M; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.; Biotechnology Doctorate Program, University of Barcelona (UB), Barcelona, Spain., Crespo A; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain., Giannotti MI; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER_BBN), Carlos III Health Institute, Madrid, Spain.; Department of Materials Science and Physical Chemistry and IQTC, University of Barcelona, Barcelona, Spain., Lagunas A; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER_BBN), Carlos III Health Institute, Madrid, Spain., Mir M; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER_BBN), Carlos III Health Institute, Madrid, Spain.; Department of Electronics and Biomedical Engineering, University of Barcelona, Barcelona, Spain., Samitier J; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER_BBN), Carlos III Health Institute, Madrid, Spain.; Department of Electronics and Biomedical Engineering, University of Barcelona, Barcelona, Spain., Muro S; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.; Institute for Bioscience and Biotechnology Research (IBBR) & Department of Chemical and Biomolecular Engineering (ChemE), University of Marylan College Park, College Park, MD, USA.; Institution of Catalonia for Research and Advanced Studies (ICREA), Barcelona, Spain. |
| Πηγή: | Journal of drug targeting [J Drug Target] 2026 Aug; Vol. 34 (7), pp. 1210-1223. Date of Electronic Publication: 2025 Dec 18. |
| Τύπος έκδοσης: | Journal Article; Research Support, N.I.H., Extramural |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Informa Healthcare Country of Publication: England NLM ID: 9312476 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1029-2330 (Electronic) Linking ISSN: 10267158 NLM ISO Abbreviation: J Drug Target Subsets: MEDLINE |
| Imprint Name(s): | Publication: London : Informa Healthcare Original Publication: Yverdon, Switzerland ; New York, NY, USA : Harwood Academic Publishers ; Reading, Berks, UK : Distributed by STBS Ltd., c1993- |
| Ιατρικοί όροι (MeSH): | Blood-Brain Barrier*/metabolism , Intercellular Adhesion Molecule-1*/metabolism , Brain*/metabolism , Drug Carriers* , Nanoparticles* , Drug Delivery Systems*, Astrocytes/metabolism ; Endothelial Cells/metabolism ; Pericytes/metabolism ; Humans ; Animals ; Lab-On-A-Chip Devices ; Microphysiological Systems ; Biological Transport |
| Περίληψη: | Targeting therapeutic nanocarriers (NCs) to endothelial receptors favours transport across the blood-brain barrier (BBB), a main obstacle to access the brain. While these strategies compel validation in animals, quantitative sub-cellular resolution is non-viable in vivo. BBB-on-chip (BBB-oC) devices can help. Illustrating this, we used a BBB-oC comprising a lateral channel containing a human brain endothelial lining and a central chamber containing hydrogel-embedded pericytes and astrocytes. We studied NCs targeting intercellular adhesion molecule-1 (ICAM-1), a cell-surface protein overexpressed in pathology and involved in CAM-mediated transport. Brain access was validated in vivo after injection of NCs coated with anti-ICAM-1 vs. control IgG. ICAM-1 expression was verified in vitro using endothelial cells, pericytes, and astrocytes (756-, 511-, 690-fold over non-specific signal under TNFα). VE-cadherin presence and lack of dextran leakage demonstrated a restrictive BBB-oC barrier. Data showed endothelial targeting of anti-ICAM-1 NCs (428 NCs/cell at 1 h), uptake (60% of cell-interacting NCs), and transcytosis (90%; 24 h) downregulated by a CAM-pathway inhibitor (88% decay; 1 h). Non-transcyosed NCs trafficked to lysosomes, while transcytosed NCs interacted with pericytes and astrocytes (2643 NCs/cell; 24 h) and entered them (90% of transcytosed NCs). This BBB-oC represents a valuable model to evaluate ICAM-1-mediated transcytosis, complementing animal studies. |
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| Grant Information: | R01 HL098416 United States HL NHLBI NIH HHS |
| Contributed Indexing: | Keywords: Blood-brain barrier; ICAM-1 targeting; endothelial and basolateral interactions; organ-on-a-chip; targeted nanocarriers; transcytosis mechanism |
| Substance Nomenclature: | 126547-89-5 (Intercellular Adhesion Molecule-1) 0 (Drug Carriers) |
| Entry Date(s): | Date Created: 20251208 Date Completed: 20260722 Latest Revision: 20260922 |
| Update Code: | 20260922 |
| PubMed Central ID: | PMC13231930 |
| DOI: | 10.1080/1061186X.2025.2600101 |
| PMID: | 41358935 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1029-2330 |
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| DOI: | 10.1080/1061186X.2025.2600101 |