In vitro microfluidic models of tumor microenvironment to screen transport of drugs and nanoparticles.

In vitro microfluidic models of tumor microenvironment to screen transport of drugs and nanoparticles.
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DOI:
10.1002/wnan.1460
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发表时间:
2017-09
期刊:
Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology
影响因子:
--
通讯作者:
Han B
Han B
中科院分区:
其他
文献类型:
--
作者:
Ozcelikkale A;Moon HR;Linnes M;Han B

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纳米技术的进步使许多类型的纳米颗粒(NP)能够改善药物向肿瘤的递送。虽然已经提出了许多NP系统,但它们的临床转化率低于预期,主要是由于目前的临床前评价技术未能充分模拟NP与肿瘤微环境的生理屏障之间的复杂相互作用。本文综述了肿瘤纳米药物微流体模型的研究进展。微流体技术通过精确控制生理线索(如静水压力、剪切应力、氧气和营养梯度)来重现肿瘤微环境,从而提供了优于传统大规模细胞培养的显著优势。微流控系统最近开始适用于在生理相关环境下筛选药物和NP。到目前为止,微流控技术在这一领域的两个主要应用领域是使用传统培养环境(如单细胞或多细胞肿瘤球体)进行高通量筛选,以及模拟肿瘤微环境以研究癌症相关的细胞-细胞和细胞-基质相互作用。这些微流体技术也可用于模拟NP递送至肿瘤的特定步骤,并通过生理条件的系统变化表征NP转运特性和结果。最终,将有可能设计出使用微流体技术为个体患者生理学量身定制的药物筛选平台。这些体外模型可以通过对癌症纳米医学进行快速和患者特异性的评估来促进精准医学的发展。
Advances in nanotechnology have enabled numerous types of nanoparticles (NPs) to improve drug delivery to tumors. While many NP systems have been proposed, their clinical translation has been less than anticipated primarily due to failure of current preclinical evaluation techniques to adequately model the complex interactions between the NP and physiological barriers of tumor microenvironment. This review focuses on microfluidic tumor models for characterization of delivery efficacy and toxicity of cancer nanomedicine. Microfluidics offer significant advantages over traditional macro-scale cell cultures by enabling recapitulation of tumor microenvironment through precise control of physiological cues such as hydrostatic pressure, shear stress, oxygen and nutrient gradients. Microfluidic systems have recently started to be adapted for screening of drugs and NPs under physiologically relevant settings. So far the two primary application areas of microfluidics in this area have been high throughput screening using traditional culture settings such as single cells or multicellular tumor spheroids, and mimicry of tumor microenvironment for study of cancer-related cell-cell and cell-matrix interactions. These microfluidic technologies are also useful in modeling specific steps in NP delivery to tumor and characterize NP transport properties and outcomes by systematic variation of physiological conditions. Ultimately, it will be possible to design drug-screening platforms uniquely tailored for individual patient physiology using microfluidics. These in vitro models can contribute to development of precision medicine by enabling rapid and patient-specific evaluation of cancer nanomedicine.
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