Simulation of complex transport of nanoparticles around a tumor using tumor-microenvironment-on-chip.
Simulation of complex transport of nanoparticles around a tumor using tumor-microenvironment-on-chip.
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DOI：
10.1016/j.jconrel.2014.08.027
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发表时间：
2014-11-28
期刊：
影响因子：
--
通讯作者：
Han B
中科院分区：
文献类型：
--
作者：
Kwak B;Ozcelikkale A;Shin CS;Park K;Han B
将治疗剂选择性地递送至肿瘤组织，这被称为“靶向递送”，是癌症治疗最热切追求的目标之一。纳米技术的最新进展使得多种类型的纳米颗粒 (NP) 成为可能，其特性可设计用于靶向递送至肿瘤。尽管早期结果令人鼓舞，但大多数纳米颗粒的递送和治疗功效仍然相当有限。这主要归因于目前可用的肿瘤模型来测试这些纳米粒子并系统地研究肿瘤周围复杂运输和病理生理障碍的影响。因此，在这项研究中，我们开发了一种新的体外肿瘤模型来概括决定肿瘤周围运输的肿瘤微环境。该模型被命名为肿瘤微环境芯片（T-MOC），由 3 维微流体通道组成，其中肿瘤细胞和内皮细胞在间质液灌注下在细胞外基质内培养。利用该T-MOC平台，研究了纳米粒子的转运及其因肿瘤微环境参数而变化，包括截止孔径、间质流体压力和肿瘤组织微观结构。结果表明，T-MOC 能够模拟肿瘤周围的复杂运输，并提供有关 NP 运输行为的详细信息。这一发现证实，纳米颗粒的设计应考虑它们与肿瘤微环境的动态相互作用。
Delivery of therapeutic agents selectively to tumor tissue, which is referred as “targeted delivery,” is one of the most ardently pursued goals of cancer therapy. Recent advances in nanotechnology enable numerous types of nanoparticles (NPs) whose properties can be designed for targeted delivery to tumors. In spite of promising early results, the delivery and therapeutic efficacy of the majority of NPs are still quite limited. This is mainly attributed to the limitation of currently available tumor models to test these NPs and systematically study the effects of complex transport and pathophysiological barriers around the tumors. In this study, thus, we developed a new in vitro tumor model to recapitulate the tumor microenvironment determining the transport around tumors. This model, named tumor-microenvironment-on-chip (T-MOC), consists of 3-dimensional microfluidic channels where tumor cells and endothelial cells are cultured within extracellular matrix under perfusion of interstitial fluid. Using this T-MOC platform, the transport of NPs and its variation due to tumor microenvironmental parameters have been studied including cut-off pore size, interstitial fluid pressure, and tumor tissue microstructure. The results suggest that T-MOC is capable of simulating the complex transport around the tumor, and providing detailed information about NP transport behavior. This finding confirms that NPs should be designed considering their dynamic interactions with tumor microenvironment.
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DOI：
10.1016/j.jconrel.2012.07.010
发表时间：
2012-12-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
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作者：
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DOI：
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发表时间：
1958-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
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影响因子：
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作者：
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通讯作者：
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