Trafficking through the blood–brain barrier is directed by core and outer surface components of layer‐by‐layer nanoparticles
Name
Bioengineering Transla Med - 2023 - Lamson - Trafficking through the blood brain barrier is directed by core and outer.pdf
Description
Published version
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6.62 MB
Format
Adobe PDF
Checksum (MD5)
701871dbe5b2e8c6ab437bb59a84182d
Author(s)
Lamson, Nicholas G
Pickering, Andrew J
Wyckoff, Jeffrey
Ganesh, Priya
Calle, Elizabeth A
Straehla, Joelle P
Hammond, Paula T
Date Issued
December 28, 2023
Journal
Bioengineering & Translational Medicine
Publisher
Wiley
Citation
Lamson, Nicholas G, Pickering, Andrew J, Wyckoff, Jeffrey, Ganesh, Priya, Calle, Elizabeth A et al. 2023. "Trafficking through the blood–brain barrier is directed by core and outer surface components of layer‐by‐layer nanoparticles." Bioengineering & Translational Medicine, 9 (4).
Version
Final published version
Abstract
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.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Broad Institute of MIT and Harvard
Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1002/btm2.10636
