Thermosensitive and Conductive Hybrid Polymer for Real-Time Monitoring of Spheroid Growth and Drug Responses.
Thermosensitive and Conductive Hybrid Polymer for Real-Time Monitoring of Spheroid Growth and Drug Responses.
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DOI：
10.1021/acssensors.0c02266
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发表时间：
2021-06-25
期刊：
影响因子：
8.9
通讯作者：
Wu T
中科院分区：
文献类型：
--
作者：
Lin ZT;Gu J;Wang H;Wu A;Sun J;Chen S;Li Y;Kong Y;Wu MX;Wu T
基于聚合物支架的三维（3D）细胞培养为模拟药物测试的生理微环境提供了一种很有前途的工具；然而，用于3D细胞培养的下一代细胞活动监测技术仍然具有挑战性。传统上，药物疗效评估和细胞生长严重依赖于细胞染色试验，使用光学设备或流式细胞术。在这里，我们报道了一种由热敏、银片和金纳米颗粒修饰的聚合物组成的双功能聚合物支架（DFPS），可以在细胞增殖或死亡时改变电导，用于原位细胞活性监测和药物筛选。通过测量聚合物网络膨胀或收缩引起的电导变化，可以定量监测细胞活性。这种新型的双功能系统(1)提供了一个三维微环境，使肿瘤球体能够在体外形成和生长，并通过热敏支架简化了肿瘤球体的收获；(2)提供了一种简单直接的定量方法来监测原位三维细胞培养的药物反应。作为概念验证，我们证明了乳腺癌干细胞系MDA-MB-436能够在支架中形成细胞球体，并且传感器的电导变化与细胞浓度呈线性关系。为了检验其在药物筛选中的潜力，我们用紫杉醇（PTX）和多西紫杉醇（DTX）处理细胞传感器中的癌球，并建立药物细胞毒性作用的预测定量评价。我们的研究结果表明，这种细胞传感系统在扩展为高通量药物筛选的阵列设备方面具有很大的潜力。
Three-dimensional (3D) cell culture based on polymer scaffold provides a promising tool to mimic a physiological microenvironment for drug testing; however, the next-generation cell activity monitoring technology for 3D cell culture is still challenging. Conventionally, drug efficacy evaluation and cell growth heavily rely on cell staining assays, using optical devices or flow cytometry. Here, we report a dual-function polymer scaffold (DFPS) composed of thermosensitive, silver flake- and gold nanoparticle-decorated polymers, enabling conductance change upon cell proliferation or death for in situ cell activity monitoring and drug screening. The cell activity can be quantitatively monitored via measuring the conductance change induced by polymeric network swelling or shrinkage. This novel dual-function system (1) provides a 3D microenvironment to enable the formation and growth of tumor spheroid in vitro and streamlines the harvesting of tumor spheroids through the thermosensitive scaffold and (2) offers a simple and direct quantitative method to monitor 3D cell culture in situ for drug responses. As a proof of concept, we demonstrated that a breast cancer stem cell line MDA-MB-436 was able to form cell spheroids in the scaffold, and the conductance change of the sensor exhibited a linear relationship with cell concentration. To examine its potential in drug screening, cancer spheroids in the cell sensor were treated with paclitaxel (PTX) and docetaxel (DTX), and predicted quantitative evaluation of the cytotoxic effect of drugs was established. Our results indicated that this cell sensing system may hold promising potential in expanding into an array device for high-throughput drug screening.
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影响因子：
4.1
作者：
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影响因子：
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作者：
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通讯作者：
Lyon, LA