Targeting of nanoparticles to the cerebral vasculature after traumatic brain injury.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Brain Injuries, Traumatic*/drug therapy ; Brain Injuries, Traumatic*/metabolism ; Brain Injuries, Traumatic*/pathology ; Vascular Cell Adhesion Molecule-1*/metabolism ; Blood-Brain Barrier*/metabolism ; Blood-Brain Barrier*/drug effects ; Nanoparticles*/chemistry; Animals ; Mice ; Liposomes ; Male ; Drug Delivery Systems ; Mice, Inbred C57BL ; Disease Models, Animal ; Endothelial Cells/metabolism ; Endothelial Cells/drug effects

Traumatic brain injury has faced numerous challenges in drug development, primarily due to the difficulty of effectively delivering drugs to the brain. However, there is a potential solution in targeted drug delivery methods involving antibody-drug conjugates or nanocarriers conjugated with targeting antibodies. Following a TBI, the blood-brain barrier (BBB) becomes permeable, which can last for years and allow the leakage of harmful plasma proteins. Consequently, an appealing approach for TBI treatment involves using drug delivery systems that utilize targeting antibodies and nanocarriers to help restore BBB integrity. In our investigation of this strategy, we examined the efficacy of free antibodies and nanocarriers targeting a specific endothelial surface marker called vascular cell adhesion molecule-1 (VCAM-1), which is known to be upregulated during inflammation. In a mouse model of TBI utilizing central fluid percussion injury, free VCAM-1 antibody did not demonstrate superior targeting when comparing sham vs. TBI brain. However, the administration of VCAM-1-targeted nanocarriers (liposomes) exhibited a 10-fold higher targeting specificity in TBI brain than in sham control. Flow cytometry and confocal microscopy analysis confirmed that VCAM-1 liposomes were primarily taken up by brain endothelial cells post-TBI. Consequently, VCAM-1 liposomes represent a promising platform for the targeted delivery of therapeutics to the brain following traumatic brain injury.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Omo-Lamai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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0 (Vascular Cell Adhesion Molecule-1)
0 (Liposomes)

Date Created: 20240610 Date Completed: 20240610 Latest Revision: 20240612

20240612

PMC11164327

10.1371/journal.pone.0297451

38857220