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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/225679
ICAM-1 Targeting of Nanocarriers in a Human Blood-Brain-Barrier-on-a-Chip Complements In Vivo Brain Delivery Observations
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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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VIGO, Marco, PALMA FLOREZ, Sujey, GRIMALT-MIRADA, Rita, PLACCI, Marina, CRESPO, Andrés, GIANNOTTI, Marina inés, LAGUNAS TARGARONA, Anna, MIR LLORENTE, Mònica, SAMITIER I MARTÍ, Josep, MURO, Silvia. ICAM-1 Targeting of Nanocarriers in a Human Blood-Brain-Barrier-on-a-Chip Complements In Vivo Brain Delivery Observations. _Journal of Drug Targeting_. 2025. [consulta: 29 de gener de 2026]. ISSN: 1061-186X. [Disponible a: https://hdl.handle.net/2445/225679]