Silica nanoconstruct cellular toleration threshold in vitro.

Silica nanoconstruct cellular toleration threshold in vitro.
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DOI:
10.1016/j.jconrel.2011.02.017
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发表时间:
2011-07-15
期刊:
Journal of controlled release : official journal of the Controlled Release Society
影响因子:
--
通讯作者:
Ghandehari H
Ghandehari H
中科院分区:
其他
文献类型:
--
作者:
Herd HL;Malugin A;Ghandehari H

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研究了二氧化硅纳米材料的几何形状对上皮细胞和吞噬细胞的细胞摄取和毒性的影响。采用改进的Stober法制备并表征了3种端氨基SiO2纳米材料:球形(178±27 nm)、蠕虫状(232±22 nm × 1348±314 nm)和圆柱状(214±29 nm × 428±66 nm)。该研究的结果表明,在该尺寸范围内,对于所研究的细胞类型,几何形状在这些颗粒的毒性和摄取模式中不起主导作用。相反,观察到所有颗粒类型的浓度阈值和细胞类型依赖性毒性。这与共聚焦显微镜观察结果相关,因为观察到所有纳米材料都被两种细胞类型吸收,在吞噬细胞中吸收程度更大。必须注意的是,似乎存在约100 µg/mL的浓度阈值,低于该浓度阈值,纳米颗粒对膜完整性、线粒体功能、吞噬作用或细胞死亡的影响有限或没有影响。通过透射电子显微镜、细胞内标记物的共定位实验和蛋白质印迹结果分析细胞形态,提供了响应于细胞内纳米颗粒积累的溶酶体逃逸、自噬样活性、隔室融合和再循环的潜在参与的证据。这些过程可能涉及细胞应对或防御机制。操纵物理化学性质以增强或降低毒性为纳米医学中使用的基于二氧化硅的纳米颗粒的安全设计铺平了道路。
The influence of geometry of silica nanomaterials on cellular uptake and toxicity on epithelial and phagocytic cells was studied. Three types of amine-terminated silica nanomaterials were prepared and characterized via the modified Stober method, namely spheres (178±27 nm), worms (232±22 nm × 1348±314 nm) and cylinders (214±29 nm × 428±66 nm). The findings of the study suggest that in this size range and for the cell types studied, geometry does not play a dominant role in the modes of toxicity and uptake of these particles. Rather, a concentration threshold and cell type dependent toxicity of all particle types was observed. This correlated with confocal microscopy observations, as all nanomaterials were observed to be taken up in both cell types, with a greater extent in phagocytic cells. It must be noted that there appears to be a concentration threshold at ~100 µg/mL, below which there is limited to no impact of the nanoparticles on membrane integrity, mitochondrial function, phagocytosis or cell death. Analysis of cell morphology by transmission electron microscopy, colocalization experiments with intracellular markers and Western Blot results provide evidence of potential involvement of lysosomal escape, autophagic like activity, compartmental fusion and recycling in response to intracellular nanoparticle accumulation. These processes could be involved in cellular coping or defense mechanisms. The manipulation of physicochemical properties to enhance or reduce toxicity paves the way for the safe design of silica-based nanoparticles for use in nanomedicine.
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