A multipurpose microfluidic device designed to mimic microenvironment gradients and develop targeted cancer therapeutics.
A multipurpose microfluidic device designed to mimic microenvironment gradients and develop targeted cancer therapeutics.
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DOI：
10.1039/b810571e
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发表时间：
2009-02-21
期刊：
影响因子：
6.1
通讯作者：
Forbes NS
中科院分区：
文献类型：
--
作者：
Walsh CL;Babin BM;Kasinskas RW;Foster JA;McGarry MJ;Forbes NS
肿瘤细胞微环境的异质性严重限制了大多数癌症治疗的疗效。我们已经设计了一种微流控设备，它模拟了肿瘤中存在的微环境梯度，将使更有效的癌症治疗方法的开发成为可能。肿瘤细胞团是在微米级的腔室内形成的，一侧暴露在介质灌流中，以产生线性营养梯度。PDMS和玻璃设备的光学可访问性使得能够对细胞团的所有区域进行定量透射式和荧光显微镜观察。使用时间推移显微镜测量生长速度，表明该装置可用于长期疗效研究。荧光显微镜显示细胞团含有活体、凋亡区和酸性区域，类似于体内肿瘤。准确测量阿霉素的扩散系数，定量治疗菌的蓄积。该装置建造简单，可以很容易地复制来制造一系列体外肿瘤。由于微环境梯度和渗透性是控制药物疗效的关键因素，我们相信这种微流控装置将对了解常见抗癌药物在实体瘤中的行为和设计新的肿瘤靶向治疗药物至关重要。
The heterogeneity of cellular microenvironments in tumors severely limits the efficacy of most cancer therapies. We have designed a microfluidic device that mimics the microenvironment gradients present in tumors that will enable the development of more effective cancer therapies. Tumor cell masses were formed within micron-scale chambers exposed to medium perfusion on one side to create linear nutrient gradients. The optical accessibility of the PDMS and glass device enables quantitative transmitted and fluorescence microscopy of all regions of the cell masses. Time-lapse microscopy was used to measure the growth rate and show that the device can be used for long-term efficacy studies. Fluorescence microscopy was used to demonstrate that the cell mass contained viable, apoptotic, and acidic regions similar to in vivo tumors. The diffusion coefficient of doxorubicin was accurately measured, and the accumulation of therapeutic bacteria was quantified. The device is simple to construct, and it can easily be reproduced to create an array of in vitro tumors. Because microenvironment gradients and penetration play critical roles controlling drug efficacy, we believe that this microfluidic device will be vital for understanding the behavior of common cancer drugs in solid tumors and designing novel intratumorally targeted therapeutics.
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影响因子：
8.8
作者：
Dewhirst, MW;Ong, ET;Braun, RD;Smith, B;Klitzman, B;Evans, SM;Wilson, D
通讯作者：
Wilson, D
DOI：
10.1124/jpet.105.099499
发表时间：
2006-05-01
影响因子：
3.5
作者：
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影响因子：
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作者：
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影响因子：
15
作者：
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通讯作者：
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影响因子：
3.8
作者：
Kim, Byoung-jin;Forbes, Neil S.
通讯作者：
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