한빛사논문
- 조회1,025
Somin Leea,†, Seongchan Kimb,†, Dong-Jun Kooc,†, James Yua, Hyeongjun Chob, Hyojin Leed, Joon Myong Songe, Sung-Yon Kimb,c,*, Dal-Hee Minb,f,*, and Noo Li Jeona,g,h,*
aProgram for Bioengineering, Seoul National University, Seoul 08826, Republic of Korea
bDepartment of Chemistry, Seoul National University, Seoul 08826, Republic of Korea
cProgram in Neuroscience, Seoul National University, Seoul 08826, Republic of Korea
dBiomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology, 5 Hwarangno 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea
eCollege of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
fInstitute of Biotherapeutics Convergence Technology, Lemonex Inc., Seoul 08826, Republic of Korea
gDepartment of Mechanical Engineering, Seoul National University, Seoul 08826, Republic of Korea
hInstitute of Advanced Machines and Design, Seoul National University, Seoul 08826, Republic of Korea
†These authors contributed equally to this work
*Corresponding Authors
Abstract
Three-dimensional (3D) visualization of tumor vasculature is a key factor in accurate evaluation of RNA interference (RNAi)-based antiangiogenic nanomedicine, a promising approach for cancer therapeutics. However, this remains challenging because there is not a physiologically relevant in vitro model or precise analytic methodology. To address this limitation, a strategy based on 3D microfluidic angiogenesis-on-a-chip and 3D tumor vascular mapping was developed for evaluating RNAi-based antiangiogenic nanomedicine. We developed a microfluidic model to recapitulate functional 3D angiogenic sprouting when co-cultured with various cancer cell types. This model enabled efficient and rapid assessment of antiangiogenic nanomedicine in treatment of hyper-angiogenic cancer. In addition, tissue-clearing-based whole vascular mapping of tumor xenograft allowed extraction of complex 3D morphological information in diverse quantitative parameters. Using this 3D imaging-based analysis, we observed tumor sub-regional differences in the antiangiogenic effect. Our systematic strategy can help in narrowing down the promising targets of antiangiogenic nanomedicine and then enables deep analysis of complex morphological changes in tumor vasculature, providing a powerful platform for the development of safe and effective nanomedicine for cancer therapeutics.
KEYWORDS : cancer angiogenesis, RNAi nanomedicine, drug efficacy evaluation, microfluidic organ-on-a-chip, 3D vascular mapping
논문정보
- Research article
- 2020년 11월 (BRIC 등록일 2020-12-11)
- 국내 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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