Ultrathin Silicon Membranes for in Situ Optical Analysis of Nanoparticle Translocation across a Human Blood-Brain Barrier Model

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Title: Ultrathin Silicon Membranes for in Situ Optical Analysis of Nanoparticle Translocation across a Human Blood-Brain Barrier Model
Authors: Hudecz, DiánaKhire, TejasChung, Hung LiAdumeau, LaurentDawson, Kenneth A.Yan, Yanet al.
Permanent link: http://hdl.handle.net/10197/12159
Date: 28-Jan-2020
Online since: 2021-05-17T15:17:16Z
Abstract: Here we present a blood-brain barrier (BBB) model that enables high-resolution imaging of nanoparticle (NP) interactions with endothelial cells and the capture of rare NP translocation events. The enabling technology is an ultrathin silicon nitride (SiN) membrane (0.5 μm pore size, 20% porosity, 400 nm thickness) integrated into a dual-chamber platform that facilitates imaging at low working distances (∼50 μm). The platform, the μSiM-BBB (microfluidic silicon membrane-BBB), features human brain endothelial cells and primary astrocytes grown on opposite sides of the membrane. The human brain endothelial cells form tight junctions on the ultrathin membranes and exhibit a significantly higher resistance to FITC-dextran diffusion than commercial membranes. The enhanced optical properties of the SiN membrane allow high-resolution live-cell imaging of three types of NPs, namely, 40 nm PS-COOH, 100 nm PS-COOH, and apolipoprotein E-conjugated 100 nm SiO2, interacting with the BBB. Despite the excellent barrier properties of the endothelial layer, we are able to document rare NP translocation events of NPs localized to lysosomal compartments of astrocytes on the "brain side" of the device. Although the translocation is always low, our data suggest that size and targeting ligand are important parameters for NP translocation across the BBB. As a platform that enables the detection of rare transmission across tight BBB layers, the μSiM-BBB is an important tool for the design of nanoparticle-based delivery of drugs to the central nervous system.
Funding Details: European Commission - Seventh Framework Programme (FP7)
Science Foundation Ireland -- replace
Funding Details: EuroNanoMed III
National Natural Science Foundation Of China
SFI-NSFC Partnership Programme
NIH
Lundbeck Foundation
Type of material: Journal Article
Publisher: ACS
Journal: ACS Nano
Volume: 14
Issue: 1
Start page: 1111
End page: 1122
Copyright (published version): 2020 American Chemical Society
Keywords: Blood-brain barrierCocultureLive-cell imagingNanoparticleUltrathin silicon nitride membraneApolipoprotein-A-IEndothelial cellsDrug deliveryVitro modelNitride membranesTranscytosisTransferrin
DOI: 10.1021/acsnano.9b08870
Language: en
Status of Item: Peer reviewed
ISSN: 1936-0851
This item is made available under a Creative Commons License: https://creativecommons.org/licenses/by-nc-nd/3.0/ie/
Appears in Collections:Centre for Bionano Interactions (CBNI) Research Collection
Conway Institute Research Collection
Biomolecular and Biomedical Science Research Collection

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