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Acta Biomater., Available online 13 October 2022 | https://doi.org/10.1016/j.actbio.2022.10.009 3D microengineered vascularized tumor spheroids for drug delivery and efficacy testing

Jungho Ahn^a,b,1, Da-Hyun Kim^c,1, Dong-Jun Koo^d,e,1, Jungeun Lim^a, Tae-Eun Park^f, Jungseub Lee^a, Jihoon Ko^a, Seongchan Kim^g, Minjae Kim^g, Kyung-Sun Kang^c, Dal-Hee Min^g, Sung-Yon Kim^d,e,g, YongTae Kim^b,h,i,j, Noo Li Jeon^a,k,l

^aDepartment of Mechanical and Aerospace Engineering, Seoul National University, Seoul 08826, Republic of Korea
^bGeorge W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
^cAdult Stem Cell Research Center and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea
^dInstitute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, South Korea
^eProgram in Neuroscience, Seoul National University, Seoul 08826, South Korea
^fUlsan National Institute of Science and Technology, Ulsan 44914, Republic of Korea
^gDepartment of Chemistry, Seoul National University, Seoul 08826, Republic of Korea
^hParker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA
ⁱInstitute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA 30332, USA
^jWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
^kDivision of WCU (World Class University) Multiscale Mechanical Design, Seoul National University, Seoul 08826, Republic of Korea
^lSeoul National University Institute of Advanced Machines and Design, Seoul 08826, Republic of Korea

¹These authors contributed equally to this work.
Corresponding authors.: Sung-Yon Kim, YongTae Kim, Noo Li Jeon

Abstract

Tumor angiogenesis is regarded as a promising target for limiting cancer progression because tumor-associated vasculature supplies blood and provides a path for metastasis. Thus, in vitro recapitulation of vascularized tumors is critical to understand the pathology of cancer and identify the mechanisms by which tumor cells proliferate, metastasize, and respond to drugs. In this study, we microengineered a vascularized tumor spheroid (VTS) model to reproduce the pathological features of solid tumors. We first generated tumor-EC hybrid spheroids with self-assembled intratumoral vessels, which enhanced the uniformity of the spheroids and peritumoral angiogenic capacity compared to spheroids composed only with cancer cells. Notably, the hybrid spheroids also exhibited expression profiles associated with aggressive behavior. The blood vessels sprouting around the hybrid spheroids on the VTS chip displayed the distinctive characteristics of leaky tumor vessels. With the VTS chip showing a progressive tumor phenotype, we validated the suppressive effects of axitinib on tumor growth and angiogenesis, which depended on exposure dose and time, highlighting the significance of tumor vascularization to predict the efficacy of anticancer drugs. Ultimately, we effectively induced both lymphangiogenesis and angiogenesis around the tumor spheroid by promoting interstitial flow. Thus, our VTS model is a valuable platform with which to investigate the interactions between tumor microenvironments and explore therapeutic strategies in cancer.

논문정보

형식Research article
게재일2022년 10월 (BRIC 등록일 2022-11-01)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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