Suyeong Seo, Seung-Yeol Nah, Kangwon Lee,* Nakwon Choi,* and Hong Nam Kim*
S. Seo, N. Choi, H. N. Kim
Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea
Program in Nano Science and Technology, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea
Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea
Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea
N. Choi, H. N. Kim
Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology (UST), Seoul 02792, Republic of Korea
KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Republic of Korea
*To whom correspondence should be addressed.
Physiologically, brain tumors interact with surrounding vascular and glial cells, and change their responses to survive in brain tissue-specific microenvironments. A major difficulty in brain tumor treatment is caused by the organism's high resistance to pharmaceutical drugs and poor blood–brain barrier (BBB) penetration. Therefore, mimicking the physiological environment of brain tumors on in vitro platforms can aid in predicting the cellular response to drugs. Here, an engineered 3D human glioblastoma in vitro platform that is integrated with a tricultured BBB is presented. First, the barrier function of the constructed BBB model and its reversibility are characterized, after administrating BBB-opening agents through the microvasculature. The brain tumor cells that are cocultured in the BBB show a more aggressive growth pattern and high drug resistance, as well as secreting high concentrations of inflammatory cytokines. Finally, the delivery of BBB-nonpenetrating drugs are promoted by chemically opening the BBB. The results of this study indicate that the platform can potentially study the physiology of the BBB, and monitor drug responses based on the interaction of the brain tumor and BBB.
Keywords : blood-brain barrier, blood-brain barrier-opening, drug delivery, in vitro model, tumor microenvironment