Cytotoxicity of surface-functionalized silicon and germanium nanoparticles: the dominant role of surface charges.

Cytotoxicity of surface-functionalized silicon and germanium nanoparticles: the dominant role of surface charges.
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DOI:
10.1039/c3nr34266b
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发表时间:
2013-06-07
期刊:
影响因子:
6.7
通讯作者:
Zuilhof H
Zuilhof H
中科院分区:
材料科学2区
文献类型:
--
作者:
Bhattacharjee S;Rietjens IM;Singh MP;Atkins TM;Purkait TK;Xu Z;Regli S;Shukaliak A;Clark RJ;Mitchell BS;Alink GM;Marcelis AT;Fink MJ;Veinot JG;Kauzlarich SM;Zuilhof H

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虽然它是假设,表面(如表面电荷)和物理特性(如粒径)在纳米粒子(NP)的细胞相互作用中发挥重要作用,探索这个问题的系统研究是缺失的。因此,使用具有各种表面官能化的广泛系列的单分散、充分表征的硅(Si)和锗(Ge)NP进行定量9种不同细胞终点的比较细胞毒性研究。采用人结肠腺癌Caco-2细胞和大鼠肺泡巨噬细胞NR 8383细胞,阐明该系列纳米粒的毒性。纳米颗粒的表面涂层似乎主导了细胞毒性:阳离子纳米颗粒表现出细胞毒性,而羧酸封端和亲水性PEG或葡聚糖封端的纳米颗粒没有。在阳离子硅纳米颗粒中,较小的硅纳米颗粒比较大的硅纳米颗粒毒性更大。掺杂锰(1%锰)的硅纳米颗粒没有表现出任何额外的毒性,这有利于它们在生物成像方面的进一步发展。铁掺杂的(1% Fe)Si NP显示出一些增加的毒性,这可能是由于Fe 3+离子从核中浸出。二氧化硅涂层似乎具有毒性,与二氧化硅的报告毒性一致。细胞内线粒体似乎是毒性纳米颗粒的靶器官,因为观察到线粒体膜电位的剂量,表面电荷和大小依赖性失衡。这种失衡导致了一系列其他细胞事件,如线粒体膜电位(Δ Km)和ATP产生降低,诱导ROS产生,细胞质Ca 2+含量增加,TNF-α产生和caspase-3活性增强。综上所述,这些结果主要通过它们的表面特性解释了Si NPs/Ge NPs的毒性,提供了对所观察到的细胞毒性的作用模式的洞察,并给出了合成生物相容性Si和Ge NPs的方向,因为这对于生物成像和例如医学领域中的其他应用至关重要。
Although it is hypothesized that surface (like surface charge) and physical characteristics (like particle size) play important roles in cellular interactions of nanoparticles (NPs), a systematic study probing this issue is missing. Hence, a comparative cytotoxicity study quantifying nine different cellular endpoints, was performed with a broad series of monodisperse, well characterized silicon (Si) and germanium (Ge) NPs with various surface functionalizations. Human colonic adenocarcinoma Caco-2 and rat alveolar macrophage NR8383 cells were used, to clarify the toxicity of this series of NPs. The surface coatings on the NPs appeared to dominate the cytotoxicity: the cationic NPs exhibited cytotoxicity, whereas the carboxylic acid-terminated and hydrophilic PEG- or dextran-terminated NPs did not. Within the cationic Si NPs, smaller Si NPs were more toxic than bigger ones. Manganese-doped (1 % Mn) Si NPs did not show any added toxicity, which favors their further development for bioimaging. Iron-doped (1 % Fe) Si NPs showed some added toxicity, which may be due to the leaching of Fe3+ ions from the core. A silica coating seemed to impart toxicity, in line with the reported toxicity of silica. Intracellular mitochondria seem to be a target organ for the toxic NPs since a dose-, surface charge- and size-dependent imbalance of the mitochondrial membrane potential was observed. Such imbalance led to a series of other cellular events for cationic NPs, like decreased mitochondrial membrane potential (ΔΨm) and ATP production, induction of ROS generation, increased cytoplasmic Ca2+ content, production of TNF-α and enhanced caspase-3 activity. Taken together, the results explain the toxicity of Si NPs/Ge NPs largely by their surface characteristics, provide insight in the mode of action underlying the observed cytotoxicity, and give directions on synthesizing biocompatible Si and Ge NPs, as this is crucial for bioimaging and other applications in for example the field of medicine.
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发表时间: 2011-05-01
期刊: ACS NANO
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