Wu Qian, Wei Xinwei, Pan Yuxiang, Zou Yingchang, Hu Ning, Wang Ping
Biosensor National Special Laboratory, Key Laboratory of Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, Zhejiang University, Hangzhou, 310027, China.
State Key Laboratory of Transducer Technology, Chinese Academy of Sciences, Shanghai, 200050, China.
Biomed Microdevices. 2018 Sep 15;20(4):82. doi: 10.1007/s10544-018-0329-x.
To perform the drug screening, planar cultured cell models are commonly applied to test efficacy and toxicity of drugs. However, planar cultured cells are different from the human 3D organs or tissues in vivo. To simulate the human 3D organs or tissues, 3D spheroids are developed by culturing a small aggregate of cells which reside around the extracellular matrix and interact with other cells in liquid media. Here we apply lung carcinoma cell lines to engineer the 3D lung cancer spheroid-based biosensor using the interdigitated electrodes for drug efficacy evaluation. The results show 3D spheroid had higher drug resistance than the planar cell model. The anticarcinogen inhibition on different 3D lung cancer spheroid models (A549, H1299, H460) can be quantitatively evaluated by electric impedance sensing. Besides, we delivered combination of anticarcinogens treatments to A549 spheroids which is commonly used in clinic treatment, and found the synergistic effect of cisplatin plus etoposide had higher drug response. To simultaneously test the drug efficacy and side effects on multi-organ model with circulatory system, a connected multiwell interdigitated electrode arraywas applied to culture different organoid spheroids. Overall, the organization of 3D cancer spheroids-based biosensor, which has higher predictive value for drug discovery and personalized medicine screening, is expected to be well applied in the area of pharmacy and clinical medicine.
为了进行药物筛选，平面培养细胞模型通常被用于测试药物的疗效和毒性。然而，平面培养细胞与体内的人体三维器官或组织不同。为了模拟人体三维器官或组织，通过培养一小团聚集在细胞外基质周围并在液体培养基中与其他细胞相互作用的细胞来构建三维球体。在这里，我们应用肺癌细胞系，使用叉指电极构建基于三维肺癌球体的生物传感器，用于药物疗效评估。结果表明，三维球体比平面细胞模型具有更高的耐药性。通过电阻抗传感可以定量评估抗癌剂对不同三维肺癌球体模型（A549、H1299、H460）的抑制作用。此外，我们将临床治疗中常用的抗癌剂联合治疗应用于A549球体，发现顺铂加依托泊苷的协同作用具有更高的药物反应。为了同时测试药物对具有循环系统的多器官模型的疗效和副作用，应用连接的多孔叉指电极阵列培养不同的类器官球体。总体而言，基于三维癌症球体的生物传感器的构建，对药物发现和个性化医学筛选具有更高的预测价值，有望在药学和临床医学领域得到很好的应用。
