Colorectal tumor-on-a-chip system: A 3D tool for precision onco-nanomedicine
Colorectal tumor-on-a-chip system: A 3D tool for precision onco-nanomedicine
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DOI：
10.1126/sciadv.aaw1317
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发表时间：
2019-05-01
期刊：
影响因子：
13.6
通讯作者：
Habibovic, P.
中科院分区：
文献类型：
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作者：
Carvalho, M. R.;Barata, D.;Habibovic, P.
传统的二维（2D）体外和非代表性动物模型可能无法完全模拟组织和器官的3D层次复杂性，这一认识正在上升。因此，后向转化为成功的临床应用受到影响。为了解决这一问题，正在开发由微流体技术驱动的芯片上仿生微环境，以更好地捕捉体内病理生理学的复杂性。在这里，我们描述了一个“芯片上的肿瘤”模型，用于评估精确的纳米药物递送，我们验证了载药纳米颗粒的疗效，在梯度的方式。通过与实时成像整合的活力研究进行模型验证，以确认暴露于CMCht/PAMAM纳米颗粒梯度的细胞的剂量-反应效应。该平台还能够在基因表达水平上进行分析，其中观察到所有研究基因（MMP-1，Caspase-3和Ki-67）的下调。这种肿瘤芯片模型代表了使用精密纳米医学进行个性化治疗的重要发展。
Awareness that traditional two-dimensional (2D) in vitro and nonrepresentative animal models may not completely emulate the 3D hierarchical complexity of tissues and organs is on the rise. Therefore, posterior translation into successful clinical application is compromised. To address this dearth, on-chip biomimetic microenvironments powered by microfluidic technologies are being developed to better capture the complexity of in vivo pathophysiology. Here, we describe a "tumor-on-a-chip" model for assessment of precision nanomedicine delivery on which we validate the efficacy of drug-loaded nanoparticles in a gradient fashion. The model validation was performed by viability studies integrated with live imaging to confirm the dose-response effect of cells exposed to the CMCht/PAMAM nanoparticle gradient. This platform also enables the analysis at the gene expression level, where a down-regulation of all the studied genes (MMP-1, Caspase-3, and Ki-67) was observed. This tumor-on-chip model represents an important development in the use of precision nanomedicine toward personalized treatment.