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UNIST, Harvard University

ACS Nano, May 22 2024, | https://doi.org/10.1021/acsnano.4c00994 Organ-on-a-Chip Approach for Accelerating Blood-Brain Barrier Nanoshuttle Discovery

Jeong-Won Choi^1,2, Kyungha Kim ¹, Karakoz Mukhambetiyar ¹, Na Kyeong Lee ³, Jonathan Sabaté Del Río ⁴, Jinmyoung Joo ^1,5,6, Chun Gwon Park ³, Taejoon Kwon ^1,5, Tae-Eun Park ¹

¹Department of Biomedical Engineering, College of Information and Biotechnology, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.

²Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Allston, Massachusetts 02134, United States.

³Department of Biomedical Engineering, Institute for Cross-disciplinary Studies (ICS), Sungkyunkwan University, Suwon, Gyeonggi 16419, Republic of Korea.

⁴Center for Algorithmic and Robotized Synthesis (CARS), Institute for Basic Science (IBS), Ulsan 44919, Republic of Korea.

⁵Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea.

⁶Graduate School of Health Science and Technology, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.

J.-W.C. and K.K. contributed equally to this work.

Corresponding Authors : Taejoon Kwon, Tae-Eun Park

Abstract

Organ-on-a-chip, which recapitulates the dynamics of in vivo vasculature, has emerged as a promising platform for studying organ-specific vascular beds. However, its practical advantages in identifying vascular-targeted drug delivery systems (DDS) over traditional in vitro models remain underexplored. This study demonstrates the reliability and efficacy of the organ-on-a-chip in screening efficient DDS by comparing its performance with that of a conventional transwell, both designed to simulate the blood-brain barrier (BBB). The BBB nanoshuttles discovered through BBB Chip-based screening demonstrated superior functionality in vivo compared to those identified using transwell methods. This enhanced effectiveness is attributed to the BBB Chip's accurate replication of the structure and dynamics of the endothelial glycocalyx, a crucial protective layer within blood vessels, especially under shear stress. This capability of the BBB Chip has enabled the identification of molecular shuttles that efficiently exploit the endothelial glycocalyx, thereby enhancing transendothelial transport efficacy. Our findings suggest that organ-on-a-chip technology holds considerable promise for advancing research in vascular-targeted DDS due to its accurate simulation of molecular transport within endothelial systems.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-05-23)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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