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Kang, Joo H.
Translational Multiscale Biofluidics Lab (TMB Lab)
Research Interests
  • Biomedical devices, infectious disease, organ-on-a-chip, microfluidics, mechanobiology

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Investigation on vascular cytotoxicity and extravascular transport of cationic polymer nanoparticles using perfusable 3D microvessel model

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Title
Investigation on vascular cytotoxicity and extravascular transport of cationic polymer nanoparticles using perfusable 3D microvessel model
Author
Ahn, JunghoCho, Chong-SuCho, Seong WooKang, Joo H.Kim, Sung-YonMin, Dal-HeeSong, Joon MyongPark, Tae-EunJeon, Noo Li
Issue Date
2018-08
Publisher
ELSEVIER SCI LTD
Citation
ACTA BIOMATERIALIA, v.76, pp.154 - 163
Abstract
Vascular networks are the first sites exposed to cationic polymer nanoparticles (NPs) administered intravenously, and thus function as a barrier for NPs reaching the target organ. While cationic polymer NPs have been intensively studied as non-viral delivery systems, their biological effects in human microvessels have been poorly investigated due to a lack of appropriate in vitro systems. Here, we employed a three-dimensional microvessel on a chip, which accurately models in vivo conditions. An open and perfused microvessel surrounded by pericytes was shown to reproduce the important features of living vasculature, including barrier function and biomarkers. Using this microvessel chip, we observed contraction of the microvascular lumen induced by perfused polyethylenimine (PEI)/DNA NPs. We demonstrated that the oxidative stress present when microvessels were exposed to PEI NPs led to rearrangement of microtubules resulting in microvessel contraction. Furthermore, the transcytotic behavior of PEI NPs was analyzed in the microvessel by monitoring the escape of PEI NPs from the microvascular lumen into the perivascular region, which was not possible in two-dimensional culture systems. With our new understanding of the different behaviors of cationic polymer NPs depending on their transcytotic route, we suggest that caveolae-mediated transcytosis is a powerful route for efficient extravascular transport.
URI
https://scholarworks.unist.ac.kr/handle/201301/24230
URL
https://www.sciencedirect.com/science/article/pii/S1742706118303179?via%3Dihub
DOI
10.1016/j.actbio.2018.05.041
ISSN
1742-7061
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