High-throughput screening with nanoimprinting 3D culture for efficient drug development by mimicking the tumor environment
High-throughput screening with nanoimprinting 3D culture for efficient drug development by mimicking the tumor environment
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DOI：
10.1016/j.biomaterials.2015.02.008
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发表时间：
2015-05-01
期刊：
影响因子：
14
通讯作者：
Saga, Tsuneo
中科院分区：
文献类型：
--
作者：
Yoshii, Yukie;Furukawa, Takako;Saga, Tsuneo
抗癌药物开发通常利用二维（2D）细胞培养的高通量筛选。然而，2D培养诱导不同于体内肿瘤的细胞特征，导致药物开发效率低下。在这里，我们报告了一种创新的高通量筛选系统，使用纳米压印3D培养来模拟体内条件，从而促进有效的药物开发。我们证明，与2D培养相比，基于细胞系的纳米压印3D筛选可以更有效地选择有效抑制体内癌症生长的药物。使用正电子发射断层扫描（PET）探针评估治疗后的代谢反应，并揭示了3D球体和体内肿瘤之间的相似特征。此外，我们开发了一种先进的方法，采用来自患者肿瘤组织的癌细胞进行纳米压印3D培养的高通量药物筛选，我们称之为癌症组织来源的均匀球体测定（COUSA）。该系统鉴定了在原始患者肿瘤的异种移植物中有效的药物。纳米压印3D球状体表现出低渗透性和内部缺氧区域的形成，类似于体内肿瘤。总的来说，纳米压印3D培养提供了易于操作的高通量药物筛选系统，该系统通过模拟肿瘤环境来进行有效的药物开发。COUSA系统可能是用患者癌细胞进行药物开发的有用平台。(C)2015爱思唯尔有限公司版权所有。
Anti-cancer drug development typically utilizes high-throughput screening with two-dimensional (2D) cell culture. However, 2D culture induces cellular characteristics different from tumors in vivo, resulting in inefficient drug development. Here, we report an innovative high-throughput screening system using nanoimprinting 3D culture to simulate in vivo conditions, thereby facilitating efficient drug development. We demonstrated that cell line-based nanoimprinting 3D screening can more efficiently select drugs that effectively inhibit cancer growth in vivo as compared to 2D culture. Metabolic responses after treatment were assessed using positron emission tomography (PET) probes, and revealed similar characteristics between the 3D spheroids and in vivo tumors. Further, we developed an advanced method to adopt cancer cells from patient tumor tissues for high-throughput drug screening with nanoimprinting 3D culture, which we termed Cancer tissue-Originated Uniformed Spheroid Assay (COUSA). This system identified drugs that were effective in xenografts of the original patient tumors. Nanoimprinting 3D spheroids showed low permeability and formation of hypoxic regions inside, similar to in vivo tumors. Collectively, the nanoimprinting 3D culture provides easy-handling high-throughput drug screening system, which allows for efficient drug development by mimicking the tumor environment. The COUSA system could be a useful platform for drug development with patient cancer cells. (C) 2015 Elsevier Ltd. All rights reserved.