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. 2021 Jul 22;11:142. doi: 10.1186/s13578-021-00650-0

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 5 — Exosomes conjugated with Br-EVs cross BBB via transcytosis. Changes in immunofluorescence intensity signal under the effects of temperature (a) transcytosis inhibition (b) and VEGF (c) in the abluminal side of the Transwell model of BBB. d Average fold change in luminescence intensity of abluminal chamber. e The effect of time changes on the fluorescence intensity of crossed Br-EVs to the abluminal side of the BBB-on-a-chip model. f Permeability changes of BBB model to 10–70 kDa dextran under the effects of Br- conjugated EVs. g Fluorescent imaging of endothelial cells with ZO-1flourescence staining and astrocytes that taking up TdTom-Br-EVs in the BBB-on-a-chip model h. Fluorescent imaging of zebrafish brain representing crossed exosomes in the brain parenchyma and the interaction of endocytic vesicles with the abluminal plasma membrane of the brain vascular endothelial cells (white arrows). i, j Distribution of 10 and 70 KDa of dextran in the zebrafish vasculature system under the effects of Br-EVs in comparison with control (PBS) groups

(Adapted with permission [72]. Copyright 2019, ACS Nano)