Engineering a Brain Cancer Chip for High-throughput Drug Screening.
Engineering a Brain Cancer Chip for High-throughput Drug Screening.
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DOI：
10.1038/srep25062
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发表时间：
2016-05-06
影响因子：
4.6
通讯作者：
Akay M
中科院分区：
文献类型：
--
作者：
Fan Y;Nguyen DT;Akay Y;Xu F;Akay M
多形性胶质母细胞瘤（GBM）是所有人类原发性脑癌中最常见和最恶性的，药物治疗仍然是最有效的治疗方法之一。然而，现有的药物发现和开发方法依赖于使用传统的二维 (2D) 细胞培养物，这已被证明不能很好地代表天然生理学。在这里，我们开发了一种由光聚合聚乙二醇二丙烯酸酯（PEGDA）水凝胶组成的新型三维（3D）脑癌芯片，用于药物筛选。这种芯片可以在几秒钟的光刻后生产出来，不需要像聚二甲基硅氧烷（PDMS）制成的微流体装置那样的硅晶片、复制成型和等离子键合。然后我们培养胶质母细胞瘤细胞（U87），使其在芯片上形成3D脑癌组织，并使用GBM芯片进行匹伐他汀和伊立替康的联合治疗。结果表明，该芯片能够进行高通量 GBM 癌症球体形成、多次同时给药以及大规模并行药物反应测试。我们的方法很容易重现，并且该芯片有潜力成为高通量药物筛选和延长药物释放等情况下的强大平台。该芯片在其他临床应用方面也具有商业前景，包括 3D 细胞培养和微型组织工程。
Glioblastoma multiforme (GBM) is the most common and malignant of all human primary brain cancers, in which drug treatment is still one of the most effective treatments. However, existing drug discovery and development methods rely on the use of conventional two-dimensional (2D) cell cultures, which have been proven to be poor representatives of native physiology. Here, we developed a novel three-dimensional (3D) brain cancer chip composed of photo-polymerizable poly(ethylene) glycol diacrylate (PEGDA) hydrogel for drug screening. This chip can be produced after a few seconds of photolithography and requires no silicon wafer, replica molding, and plasma bonding like microfluidic devices made of poly(dimethylsiloxane) (PDMS). We then cultured glioblastoma cells (U87), which formed 3D brain cancer tissues on the chip, and used the GBM chip to perform combinatorial treatment of Pitavastatin and Irinotecan. The results indicate that this chip is capable of high-throughput GBM cancer spheroids formation, multiple-simultaneous drug administration, and a massive parallel testing of drug response. Our approach is easily reproducible, and this chip has the potential to be a powerful platform in cases such as high-throughput drug screening and prolonged drug release. The chip is also commercially promising for other clinical applications, including 3D cell culture and micro-scale tissue engineering.