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Generation of High-Throughput Three-Dimensional Tumor Spheroids for Drug Screening
Published on: September 5, 2018
Vertically Coated Graphene Oxide Micro-Well Arrays for Highly Efficient Cancer Spheroid Formation and Drug Screening
Cheol-Hwi Kim1, Intan Rosalina Suhito1, Novi Angeline1
1School of Integrative Engineering, Chung-Ang University, Seoul, 06974, Republic of Korea.
Abstract:
Research on the 3D culturing of cancer cells that better mimic in vivo solid tumors is important for efficient drug screening. Herein, a new platform that effectively facilitates the formation of cancer spheroids for anticancer drug screening is reported. Cytophilic graphene oxide (GO), when selectively coated on the sidewalls of micro-wells fabricated from a cell-adhesion-resistive polymer, is found to efficiently initiates distinct donut-like formation of cancer cell spheroids. Scanning electron microscopy and Raman mapping are used to analyze vertically coated GO micropatterns (vGO-MPs) of different sizes (100-250 µm) on polymer platforms, and human liver cancer cells (HepG2), as a model cancer, are seeded on these platforms. Remarkably, the 150 µm-sized platform is found to easily and rapidly generate 3D spheroids in the absence of cell-adhesion proteins. In addition, owing to the unique characteristics of GO, vGO-MPs are highly stable for long periods of time (≈1 month), even under harsh conditions (>70 °C). Moreover, the anticancer effects of two drugs (hydroxyurea and cisplatin) and the potential anticancer compound (curcumin) on HepG2 cells are demonstrated by simply measuring decreases in spheroid sizes. Hence, this new platform is highly promising as a cancer spheroid-forming material for rapid drug screening.
Insights
A novel graphene oxide (GO) platform efficiently forms 3D cancer spheroids for drug screening. This 3D cell culture method accelerates the discovery of new anticancer drugs.
Area of Science:
- Biomaterials Engineering
- Cancer Research
- Drug Discovery
Background:
- 3D cancer cell cultures better mimic in vivo tumors than 2D models.
- Efficient drug screening requires models that accurately represent tumor microenvironments.
Purpose of the Study:
- To develop a new platform for rapid formation of cancer spheroids for anticancer drug screening.
- To utilize cytophilic graphene oxide (GO) for controlled spheroid formation.
Main Methods:
- Fabrication of micro-wells from cell-adhesion-resistive polymer with selectively coated GO sidewalls.
- Analysis of vertically coated GO micropatterns (vGO-MPs) using scanning electron microscopy and Raman mapping.
- Seeding of human liver cancer cells (HepG2) on the platform to form 3D spheroids.
Main Results:
- The 150 µm GO-coated platform rapidly generated distinct donut-like cancer spheroids without cell-adhesion proteins.
- vGO-MPs demonstrated high stability (≈1 month) under harsh conditions (>70 °C).
- Anticancer effects of hydroxyurea, cisplatin, and curcumin were evaluated by measuring spheroid size reduction.
Conclusions:
- The developed GO-based platform effectively facilitates 3D cancer spheroid formation.
- This platform shows high promise for rapid and efficient anticancer drug screening.
- The stability and ease of use make it suitable for various drug testing applications.

