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用于筛选神经相关抗癌药物的微图案共培养平台

Micropatterned Coculture Platform for Screening Nerve-Related Anticancer Drugs.

作者信息

Liu Xiaoyan, Zhang Wei, Zheng Wenfu, Jiang Xingyu

机构信息

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, No. 11 Zhongguancun Beiyitiao, Beijing 100190, P. R. China.

Department of Biomedical Engineering, Southern University of Science and Technology, No. 1088 Xueyuan Road, Xili, Nanshan District, Shenzhen, Guangdong 518055, P. R. China.

出版信息

ACS Nano. 2021 Jan 26;15(1):637-649. doi: 10.1021/acsnano.0c06416. Epub 2021 Jan 13.

Abstract

Accumulating evidence suggests that the neural microenvironment plays a vital role in the development and metastasis of cancers. The development of drug candidates or drug combinations targeting the neural microenvironment is thus becoming increasingly urgent. However, the low content of conventional drug screening platforms is a bottleneck that limits the drug evaluation process. In this study, we present a micropatterned coculture-based high-content (μCHC) platform by integrating a micropatterned coculture chip with the high-content analysis (HCA) system, for studying the neuron-cancer cell interactions and drug screening (simultaneously detecting 96 kinds of post-drug-treated conditions). We investigate the contribution of neurons on the migration of cancer cells from different tissues and validate the capability of the μCHC system to study the interaction between neurons and cancer cells. Moreover, we test the effects of individual or combinatory agents targeting the neuron or cancer cell on the neuron-cancer cell interactions, which proposes an optimized therapy regime for targeting both nervous and cancerous factors. Our study suggests that the μCHC system is a facile platform for screening drug candidates or drug combinations for clinical cancer therapy with high efficiency and fidelity.

摘要

越来越多的证据表明,神经微环境在癌症的发生和转移中起着至关重要的作用。因此,开发针对神经微环境的候选药物或药物组合变得越来越迫切。然而,传统药物筛选平台的低通量是限制药物评估过程的一个瓶颈。在本研究中,我们通过将微图案共培养芯片与高通量分析(HCA)系统相结合,提出了一种基于微图案共培养的高通量(μCHC)平台,用于研究神经元与癌细胞的相互作用和药物筛选(同时检测96种药物处理后的条件)。我们研究了神经元对不同组织来源癌细胞迁移的影响,并验证了μCHC系统研究神经元与癌细胞相互作用的能力。此外,我们测试了针对神经元或癌细胞的单一或联合药物对神经元-癌细胞相互作用的影响,从而提出了一种针对神经和癌症因素的优化治疗方案。我们的研究表明,μCHC系统是一个简便的平台,可高效、准确地筛选用于临床癌症治疗的候选药物或药物组合。

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