Laboratory of Organic Chemistry, Wageningen University, Dreijenplein 8, 6703 HB Wageningen, The Netherlands.
Nanoscale. 2013 Jun 7;5(11):4870-83. doi: 10.1039/c3nr34266b. Epub 2013 Apr 25.
Although it is frequently 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 Fe(3+) ions from the core. A silica coating seemed to impart toxicity, in line with the reported toxicity of silica. Intracellular mitochondria seem to be the target for the toxic NPs since a dose-, surface charge- and size-dependent imbalance of the mitochondrial membrane potential was observed. Such an 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 Ca(2+) 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 into 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.
虽然人们经常假设表面（如表面电荷）和物理特性（如粒径）在纳米颗粒（NPs）的细胞相互作用中起着重要作用，但缺少对此问题的系统研究。因此，进行了一项比较细胞毒性的研究，使用具有各种表面功能化的广泛系列单分散、特征良好的硅（Si）和锗（Ge）纳米颗粒，量化了 9 种不同的细胞终点。使用人结肠腺癌细胞 Caco-2 和大鼠肺泡巨噬细胞 NR8383 细胞来阐明该系列纳米颗粒的毒性。纳米颗粒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，而羧酸末端和亲水性 PEG 或葡聚糖末端的纳米颗粒则没有。在阳离子 Si NPs 中，较小的 Si NPs 比较大的 Si NPs 毒性更大。未显示出任何额外毒性的 Mn 掺杂（1%Mn）Si NPs 有利于其进一步开发用于生物成像。具有一些额外毒性的 Fe 掺杂（1%Fe）Si NPs 可能是由于核心中的 Fe(3+)离子浸出所致。硅涂层似乎具有毒性，这与报道的二氧化硅毒性一致。细胞内的线粒体似乎是有毒纳米颗粒的靶标，因为观察到线粒体膜电位的剂量、表面电荷和尺寸依赖性失衡。这种失衡导致阳离子 NPs 发生一系列其他细胞事件，如线粒体膜电位（ΔΨm）和 ATP 产生减少、ROS 生成诱导、细胞质 Ca(2+)含量增加、TNF-α 产生和 caspase-3 活性增强。总之，这些结果主要通过纳米颗粒的表面特性解释了 Si NPs/Ge NPs 的毒性，深入了解了观察到的细胞毒性的作用模式，并为合成生物相容性 Si 和 Ge NPs 指明了方向，因为这对于生物成像和医学等领域的其他应用至关重要。
