Cell compatibility of a maghemite/polymer biomedical nanoplatform
Cell compatibility of a maghemite/polymer biomedical nanoplatform
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DOI：
10.1016/j.tiv.2015.04.003
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发表时间：
2015-08-01
影响因子：
3.2
通讯作者：
Sorribas, Victor
中科院分区：
文献类型：
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作者：
Ali, Lamiaa M. A.;Pinol, Rafael;Sorribas, Victor
我们报告的细胞相容性和细胞命运的氧化铁/聚合物纳米平台（IONP）在其最基本的配方，使用间充质（血管平滑肌细胞，VSMC）和上皮（负鼠肾，OK）细胞。纳米平台的细胞毒性和细胞内化与暴露时间和不同组分的浓度有关。研究了一系列具有不同氧化铁纳米颗粒、尺寸、流体力学尺寸和铁/聚合物比的样品。在所有情况下，细胞毒性是低的，它主要是由内化率，在VSMC中高于OK细胞。平均致死剂量具有非常窄的阈值，并且坏死是唯一的细胞死亡类型。IONP摄取对氧化应激的影响很小，仅在高浓度下用较小的IONP观察到炎性小体活化。VSMC的内化速率完全由聚合物浓度决定。在OK细胞中，内化率似乎随着流体动力学尺寸的减小而增加。内化通过网格蛋白依赖性内吞作用发生，因为它被钾耗竭和氯丙嗪阻止。IONP被定向并积聚在溶酶体中。在IONP超负荷下，溶酶体功能障碍将导致细胞死亡，使用在体内难以达到的浓度。(C)2015爱思唯尔有限公司版权所有。
We are reporting the cytocompatibility and cellular fate of an iron oxide/polymer nanoplatform (IONP) in its most basic formulation, using both mesenchymal (vascular smooth muscle cells, VSMC), and epithelial (opossum kidney, OK) cells. The cytotoxicity and cell internalization of the nanoplatform has been evaluated in relation to time of exposure and concentration of different components. A series of samples with different iron oxide nanoparticle, sizes, hydrodynamic sizes and iron/polymer ratio have been examined. In all cases cytotoxicity is low, and it is mostly determined by the internalization rate, being higher in VSMC than in OK cells. The mean lethal dose has a very narrow threshold, and necrosis is the only cell death type. IONP uptake shows little incidence on oxidative stress, and inflammasome activation is only observed with the smaller IONP at high concentration. The internalization rate in VSMC is determined by the polymer concentration exclusively. In OK cells, internalization rate seems to increase with decreasing hydrodynamic size. Internalization occurs through clathrin-dependent endocytosis, as it is prevented by potassium depletion and chlorpromazine. IONP are directed and accumulated in lysosomes. Under IONP overload, lysosomal dysfunction would cause cell death using concentrations that are hardly achieved in vivo. (C) 2015 Elsevier Ltd. All rights reserved.