Trafficking through the blood–brain barrier is directed by core and outer surface components of layer‐by‐layer nanoparticles

Drug‐carrying nanoparticles are a promising strategy to deliver therapeutics into the brain, but their translation requires better characterization of interactions between nanomaterials and endothelial cells of the blood–brain barrier (BBB). Here, we use a library of 18 layer‐by‐layer electrostatica...

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Published inBioengineering & translational medicine Vol. 9; no. 4; pp. e10636 - n/a
Main Authors Lamson, Nicholas G., Pickering, Andrew J., Wyckoff, Jeffrey, Ganesh, Priya, Calle, Elizabeth A., Straehla, Joelle P., Hammond, Paula T.
Format Journal Article
LanguageEnglish
Published Hoboken, USA John Wiley & Sons, Inc 01.07.2024
Wiley
Subjects
Blood vessels
Blood-brain barrier
Brain cancer
Cells
drug delivery
Endothelial cells
Flow cytometry
Fluid flow
Gene expression
Hyaluronic acid
in vitro models
In vivo methods and tests
intracellular trafficking
intravital imaging
layer‐by‐layer
Nanomaterials
Nanoparticles
Permeability
Polyesters
Surface chemistry
blood–brain barrier
nanoparticles
in vitro models
intracellular trafficking
drug delivery
intravital imaging
layer‐by‐layer
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Summary:Drug‐carrying nanoparticles are a promising strategy to deliver therapeutics into the brain, but their translation requires better characterization of interactions between nanomaterials and endothelial cells of the blood–brain barrier (BBB). Here, we use a library of 18 layer‐by‐layer electrostatically assembled nanoparticles (NPs) to independently assess the impact of NP core and surface materials on in vitro uptake, transport, and intracellular trafficking in brain endothelial cells. We demonstrate that NP core stiffness determines the magnitude of transport, while surface chemistry directs intracellular trafficking. Finally, we demonstrate that these factors similarly dictate in vivo BBB transport using intravital imaging through cranial windows in mice. We identify that hyaluronic acid surface chemistry increases transport across the BBB in vivo, and flow conditions are necessary to replicate this finding in vitro. Taken together, these findings highlight the importance of assay geometry, cell biology, and fluid flow in developing nanocarriers for delivery to the brain.
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ISSN:2380-6761
2380-6761
DOI:10.1002/btm2.10636