Core material and surface chemistry of Layer-by-Layer (LbL) nanoparticles independently direct uptake, transport, and trafficking in preclinical blood-brain barrier (BBB) models
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Le résumé fourni par la source
Abstract Development of new treatments for neurological disorders, especially brain tumors and neurodegenerative diseases, is hampered by poor accumulation of new therapeutic candidates in the brain. Drug carrying nanoparticles are a promising strategy to deliver therapeutics, but there is a major need to understand interactions between nanomaterials and the cells of the blood-brain barrier (BBB), and to what degree these interactions can be predicted by preclinical models. Here, we use a library of eighteen layer-by-layer electrostatically assembled nanoparticles (LbL-NPs) to independently assess the impact of nanoparticle core stiffness and surface chemistry on in vitro uptake and transport in three common assays, as well as intracellular trafficking in hCMEC/D3 endothelial cells. We demonstrate that nanoparticle core stiffness impacts the magnitude of material transported, while surface chemistry influences how the nanoparticles are trafficked within the cell. Finally, we demonstrate that these factors similarly dictate in vivo BBB transport using intravital imaging through cranial windows in mice, and we discover that a hyaluronic acid surface chemistry provides an unpredicted boost to transport. Taken together, these findings highlight the importance of considering factors such as assay geometry, nanomaterial labelling strategies, and fluid flow in designing preclinical assays to improve nanoparticle screening throughput for drug delivery to the brain.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Core material and surface chemistry of Layer-by-Layer (LbL) nanoparticles independently direct uptake, transport, and trafficking in preclinical blood-brain barrier (BBB) models
- Date Crossref
- 01/11/2022
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Massachusetts Institute of Technology Department of Chemical Engineering pays non établi dans la noticeUniversité ou école supérieure
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Boston Children's Hospital Division of Pediatric Hematology/Oncology pays non établi dans la noticeÉtablissement de santé
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Dana-Farber Cancer Institute Department of Pediatric Oncology pays non établi dans la noticeStructure de recherche
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Broad Institute pays non établi dans la noticeOrganisation à but non lucratif
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Institute for Soldier Nanotechnologies pays non établi dans la noticeStructure de recherche
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Koch Institute for Integrative Cancer Research pays non établi dans la noticeStructure de recherche
Department of Chemical Engineering — Massachusetts Institute of Technology, Division of Pediatric Hematology/Oncology — Boston Children's Hospital et Department of Pediatric Oncology — Dana-Farber Cancer Institute, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.