Synthetic tumor networks for screening drug delivery systems.
Synthetic tumor networks for screening drug delivery systems.
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DOI：
10.1016/j.jconrel.2015.01.018
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发表时间：
2015-03-10
影响因子：
10.8
通讯作者：
Pant, Kapil
中科院分区：
文献类型：
--
作者：
Prabhakarpandian, Balabhaskar;Shen, Ming-Che;Nichols, Joseph B.;Garson, Charles J.;Mills, Ivy R.;Matar, Majed M.;Fewell, Jason G.;Pant, Kapil
肿瘤给药是一种除药物或给药载体的物理化学性质外，还受多种因素影响的复杂现象。一个关键因素是肿瘤微血管，它具有复杂的效应，包括对流传输、高间质压力和由于“泄漏血管”的存在而导致的血管通透性增加。目前用于评价药物释放的肿瘤微环境的体外模型过于简化，因此与体内表现的相关性很差。在这项研究中，我们报告了一种新型微流控平台的开发，该平台可以更准确地模拟肿瘤微环境，具有生理和形态上真实的微血管，包括内皮细胞衬里的泄漏毛细血管和3D实体肿瘤。血管内皮细胞和宫颈肿瘤细胞的3D球体在网络中共培养。通过不同配方的纳米聚合物，利用GFP基因传递技术对药物载体进行筛选。合成肿瘤网络成功地预测了药物载体的体内递送效率。所开发的分析方法将在基础研究和药物发现方面都有重要的应用，在基础研究中，它可以用来开发下一代给药载体，在药物发现中，它可以用来研究现实肿瘤微环境中的药物传输和给药效率，从而使药物化合物和/或给药载体的筛选成为可能。
Tumor drug delivery is a complex phenomenon affected by several elements in addition to drug or delivery vehicle’s physico-chemical properties. A key factor is tumor microvasculature with complex effects including convective transport, high interstitial pressure and enhanced vascular permeability due to the presence of “leaky vessels”. Current in vitro models of the tumor microenvironment for evaluating drug delivery are oversimplified and, as a result, show poor correlation with in vivo performance. In this study, we report on the development of a novel microfluidic platform that models the tumor microenvironment more accurately, with physiologically and morphologically realistic microvasculature including endothelial cell lined leaky capillary vessels along with 3D solid tumors. Endothelial cells and 3D spheroids of cervical tumor cells were co-cultured in the networks. Drug vehicle screening was demonstrated using GFP gene delivery by different formulations of nanopolymers. The synthetic tumor network was successful in predicting in vivo delivery efficiencies of the drug vehicles. The developed assay will have critical applications both in basic research, where it can be used to develop next generation delivery vehicles, and in drug discovery where it can be used to study drug transport and delivery efficacy in realistic tumor microenvironment, thereby enabling drug compound and/or delivery vehicle screening.
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影响因子：
14
作者：
Hsiao, Amy Y.;Torisawa, Yu-suke;Tung, Yi-Chung;Sud, Sudha;Taichman, Russell S.;Pienta, Kenneth J.;Takayama, Shuichi
通讯作者：
Takayama, Shuichi
影响因子：
10.8
作者：
Champion, Julie A.;Katare, Yogesh K.;Mitragotri, Samir
通讯作者：
Mitragotri, Samir
影响因子：
10.3
作者：
Dreher, MR;Liu, WG;Chilkoti, A
通讯作者：
Chilkoti, A
影响因子：
3.6
作者：
Khare R;Chen CY;Weaver EA;Barry MA
通讯作者：
Barry MA
影响因子：
5.1
作者：
Anwer, K.;Barnes, M. N.;Alvarez, R. D.
通讯作者：
Alvarez, R. D.