Biomimicry 3D Gastrointestinal Spheroid Platform for the Assessment of Toxicity and Inflammatory Effects of Zinc Oxide Nanoparticles
Biomimicry 3D Gastrointestinal Spheroid Platform for the Assessment of Toxicity and Inflammatory Effects of Zinc Oxide Nanoparticles
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DOI：
10.1002/smll.201401915
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发表时间：
2015-02-11
期刊：
影响因子：
13.3
通讯作者：
Leong, David T.
中科院分区：
文献类型：
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作者：
Chia, Sing Ling;Tay, Chor Yong;Leong, David T.
我们目前对工程纳米颗粒（NPs）对细胞生理学影响的机制理解主要来自二维细胞培养研究。然而，传统的单层细胞培养可能不能准确地模拟3D组织生理学中预期的传质梯度，因此可能导致人为的实验结论。本文利用微图案琼脂糖水凝胶平台，研究了氧化锌纳米粒子（25 nm）对三维结肠细胞球体的影响。研究结果表明，细胞维度在控制ZnO NPs处理的时空细胞结果（如炎症反应和细胞毒性）中起着关键作用。更重要的是，ZnO NPs可以在2D和3D细胞培养系统中诱导不同模式的细胞死亡。有趣的是，在3D模型中，外层的几层细胞只能在有限的时间内保护细胞的内核，并周期性地从球体表面脱落。这些发现表明，通过二维细胞模型得出的毒理学结论可能高估了ZnO NPs的毒性。这种三维细胞球体模型可以作为一个可复制的平台，更好地反映细胞对纳米颗粒的实际反应，并研究更现实的纳米颗粒诱导毒性机制。
Our current mechanistic understanding on the effects of engineered nanoparticles (NPs) on cellular physiology is derived mainly from 2D cell culture studies. However, conventional monolayer cell culture may not accurately model the mass transfer gradient that is expected in 3D tissue physiology and thus may lead to artifactual experimental conclusions. Herein, using a micropatterned agarose hydrogel platform, the effects of ZnO NPs (25 nm) on 3D colon cell spheroids of well-defined sizes are examined. The findings show that cell dimensionality plays a critical role in governing the spatiotemporal cellular outcomes like inflammatory response and cytotoxicity in response to ZnO NPs treatment. More importantly, ZnO NPs can induce different modes of cell death in 2D and 3D cell culture systems. Interestingly, the outer few layers of cells in 3D model could only protect the inner core of cells for a limited time and periodically slough off from the spheroids surface. These findings suggest that toxicological conclusions made from 2D cell models might overestimate the toxicity of ZnO NPs. This 3D cell spheroid model can serve as a reproducible platform to better reflect the actual cell response to NPs and to study a more realistic mechanism of nanoparticle-induced toxicity.