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Near-physiological microenvironment simulation on chip to evaluate drug resistance of different loci in tumour mass
Talanta ( IF 5.6 ) Pub Date : 2018-08-11 , DOI: 10.1016/j.talanta.2018.08.016
Shiqi Wang , Sifeng Mao , Min Li , Hai-Fang Li , Jin-Ming Lin

Developing a bio-functional model in vitro to study cancer resistance, which is a big challenge for clinical cancer therapy, is of great interest. Such reliable model requires appropriate drug diffusion kinetics simulation and a microenvironment that allows cell-cell and cell-matrix interactions. In this work, a special hydrogel-based three-dimensional (3D) microfluidic chip was constructed to simulate tumour-vascular microenvironment. The self-healing hydrogel supports long-time cell survival and proliferation, effective cellular metabolism of cancer drugs and cell-cell interaction between different types of cells. In the effective near-physiological tumour-vascular microenvironment, the endothelial and fibroblast cells are spread on different sides of a porous membrane, while sensitive and resistant breast tumour cells are separately cultured in the dynamic hydrogel consisting of glycol chitosan and telechelic difunctional poly (ethylene glycol) in the upper chambers. Nutrients and drugs are introduced through the bottom channel and diffuse into the cancer cells. Doxorubicin molecules pass first through blood vessel endothelial cells and act on the tumour cells surrounded by fibroblasts. Tumour cells respond differently to drug when they are cultured in the microenvironment. Sensitive breast tumour cells have a 47% increase in viability than those cultured without fibroblasts and endothelial cells. Both sensitive and resistant tumour cells can be analysed under the same chemical environment. This work represents a multi-functional in vitro platform that allows near-physiological simulation, effective drug metabolism and cellular response to extracellular stimuli and has great potential to make drug discovery speedy and precise.



中文翻译:

芯片上近生理微环境模拟,评估肿瘤块中不同基因座的耐药性

体外建立生物功能模型研究抗癌性是临床癌症治疗的一大挑战,这一点引起了人们的极大兴趣。这种可靠的模型需要适当的药物扩散动力学模拟和允许细胞-细胞和细胞-基质相互作用的微环境。在这项工作中,构建了一种特殊的基于水凝胶的三维(3D)微流控芯片,以模拟肿瘤-血管微环境。自愈水凝胶支持长期的细胞存活和增殖,抗癌药物的有效细胞代谢以及不同类型细胞之间的细胞间相互作用。在有效的近生理肿瘤血管微环境中,内皮细胞和成纤维细胞分布在多孔膜的不同侧,而敏感性和耐药性的乳腺癌细胞则分别在上腔中的乙二醇壳聚糖和远螯双官能聚乙二醇组成的动态水凝胶中培养。营养物质和药物通过底部通道引入并扩散到癌细胞中。阿霉素分子首先穿过血管内皮细胞,并作用于被成纤维细胞包围的肿瘤细胞上。在微环境中培养时,肿瘤细胞对药物的反应不同。敏感的乳腺肿瘤细胞的存活力比不含成纤维细胞和内皮细胞的乳腺癌细胞的存活力提高了47%。敏感和耐药的肿瘤细胞都可以在相同的化学环境下进行分析。这项工作代表了多功能 营养物质和药物通过底部通道引入并扩散到癌细胞中。阿霉素分子首先穿过血管内皮细胞,并作用于被成纤维细胞包围的肿瘤细胞上。在微环境中培养时,肿瘤细胞对药物的反应不同。敏感的乳腺肿瘤细胞比没有成纤维细胞和内皮细胞培养的细胞活力提高了47%。敏感和耐药的肿瘤细胞都可以在相同的化学环境下进行分析。这项工作代表了多功能 营养物质和药物通过底部通道引入并扩散到癌细胞中。阿霉素分子首先穿过血管内皮细胞,并作用于被成纤维细胞包围的肿瘤细胞上。在微环境中培养时,肿瘤细胞对药物的反应不同。敏感的乳腺肿瘤细胞比没有成纤维细胞和内皮细胞培养的细胞活力提高了47%。敏感和耐药的肿瘤细胞都可以在相同的化学环境下进行分析。这项工作代表了多功能 在微环境中培养时,肿瘤细胞对药物的反应不同。敏感的乳腺肿瘤细胞比没有成纤维细胞和内皮细胞培养的细胞活力提高了47%。敏感和耐药的肿瘤细胞都可以在相同的化学环境下进行分析。这项工作代表了多功能 在微环境中培养时,肿瘤细胞对药物的反应不同。敏感的乳腺肿瘤细胞比没有成纤维细胞和内皮细胞培养的细胞活力提高了47%。敏感和耐药的肿瘤细胞都可以在相同的化学环境下进行分析。这项工作代表了一项多功能体外平台,可以进行近乎生理的模拟,有效的药物代谢和细胞对细胞外刺激的反应,并具有使药物发现迅速而精确的巨大潜力。

更新日期:2018-08-11
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