Protein Corona Mediated Uptake and Cytotoxicity of Silver Nanoparticles in Mouse Embryonic Fibroblast
Protein Corona Mediated Uptake and Cytotoxicity of Silver Nanoparticles in Mouse Embryonic Fibroblast
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DOI：
10.1002/smll.201801219
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发表时间：
2018-08-23
期刊：
影响因子：
13.3
通讯作者：
Gentili, Denis
中科院分区：
文献类型：
--
作者：
Barbalinardo, Marianna;Caicci, Federico;Gentili, Denis
纳米粒子（NPs）的医学应用需要了解它们与生命系统的相互作用，以控制它们的生理反应，如细胞摄取和细胞毒性。当纳米颗粒暴露于生物液体时，细胞外蛋白质在纳米颗粒表面的吸附，产生所谓的蛋白质冠，可以严重影响它们与细胞的相互作用。在这里，表面涂层的银纳米粒子（AgNPs）的血清蛋白（SP）的吸附和其后果的细胞摄取和细胞毒性在小鼠胚胎成纤维细胞的效果。特别是，柠檬酸盐封端的银纳米颗粒被细胞内化，并显示出时间和剂量依赖性的毒性，而用低聚（乙二醇）（OEG）-烷醇的NP表面的钝化大大降低了它们的摄取和细胞毒性。暴露于含有SP的生长培养基揭示了柠檬酸盐封端的AgNP被蛋白质迅速包被和稳定，而由用OG-烷乙醇胺封端产生的AgNP更能抵抗蛋白质吸附到其表面上。使用在无血清中培养的NIH-3 T3，显示SP吸附到NP表面上的关键作用，因为只有具有预先形成的蛋白质冠的AgNP可以被细胞内化，因此，执行其固有的细胞毒性活性。
Medical applications of nanoparticles (NPs) require understanding of their interactions with living systems in order to control their physiological response, such as cellular uptake and cytotoxicity. When NPs are exposed to biological fluids, the adsorption of extracellular proteins on the surface of NPs, creating the so-called protein corona, can critically affect their interactions with cells. Here, the effect of surface coating of silver nanoparticles (AgNPs) on the adsorption of serum proteins (SPs) and its consequence on cellular uptake and cytotoxicity in mouse embryonic fibroblasts are shown. In particular, citrate-capped AgNPs are internalized by cells and show a time- and dose-dependent toxicity, while the passivation of the NP surface with an oligo(ethylene glycol) (OEG)-alkanethiol drastically reduces their uptake and cytotoxicity. The exposure to growth media containing SPs reveals that citrate-capped AgNPs are promptly coated and stabilized by proteins, while the AgNPs resulting from capping with the OEG-alkanethiol are more resistant to adsorption of proteins onto their surface. Using NIH-3T3 cultured in serum-free, the key role of the adsorption of SPs onto surface of NPs is shown as only AgNPs with a preformed protein corona can be internalized by the cells and, consequently, carry out their inherent cytotoxic activity.