Nanomaterial-modified hybrid platforms for highly efficient
cancer spheroid formation and drug screening
Tae-Hyung Kim
School of Integrative Engineering, Chung-Ang University, Seoul, Korea; Integrative Research Center for Two‐Dimensional Functional Materials, Institute of Interdisciplinary Convergence Research, Chung-Ang University, Seoul, Korea
thkim0512@cau.ac.kr
Abstract
Recently, three-dimensional in vitro cell culture has been emerged as a method to better mimic in vivo solid tumors and their microenvironment. Here, we report a new type of platform that enables both highly efficient cancer spheroid formation and rapid drug testing. Graphene oxide was chosen as a key nanomaterial and selectively coated onto the sidewall of each cell-adhesion-repulsive micro-well (vGO-MP), which prevents planar cell growth and forces the vertical expansion of the cancer cells. Using this platform, various cancer cell spheroids (e.g. liver cancer, neuroblastoma, and glioblastoma) with uniform size and shape were generated. Moreover, due to spheroid-size and array uniformities, the effects of various anticancer compounds (e.g. cisplatin, hydroxyl urea, and curcumin) on cell viability were effectively assessed based on the reductions in the sizes of each spheroid. Besides an attempt to generate cancer spheroids in a highly efficient manner, precise detection of spheroids viability is another important issue for drug screening. Interestingly, we found that a highly conductive gold nanostructure (HCGN) generated on a transparent electrode surface is effective in generating multicellular brain cancer spheroids, and is also capable of measuring spheroids viability based on the electrochemical detection method. We have previously reported the cell type-specific redox signals are extremely sensitive to the changes in cell viability. Remarkably, such electrochemical signals of cancer cells were also found to be highly sensitive to measure cell viability in three-dimensional (3D) spheroids than conventional colorimetric assay under drug treatment conditions. Specifically, a decrease in 3D spheroid cell viability at a low curcumin concentration (30 µM) was detectable using this new method (29.4%) but not with a conventional colorimetric assay. Taken together, it can be concluded that the nanohybrid platforms developed by our group are highly promising for rapid and precise anticancer drug screening based on 3D and multicellular cancer models.
Short Bio
Tae-Hyung Kim is a director of Bionano Engineering and Sensing Technology (BEST) Laboratory and an associate professor of the School of Integrative Engineering at Chung-Ang University, Seoul, Korea. He received his B.S. in Chemical Engineering from Sogang University and a Ph.D. in Chemical and Biomolecular Engineering from Sogang University. He was a postdoctoral researcher of the Department of Chemistry and Chemical Biology, Rutgers University, U.S.A. His research focus is in the area of cellular engineering, with a particular focus on the use of various nanomaterials to control and to monitor cellular behaviors in a non-destructive and non-invasive manner. He has published over 65 peer-reviewed articles, over 50 presentations with over 30 invited presentations. He holds journal editorial board memberships of several international journals including Managing Editor of Nano Convergence, Associate Editor of Biochip Journal, and Editorial Board Member of Biotechnology and Bioprocess Engineering.