Department of Pharmaceutics and Pharmaceutical Chemistry, Nano Institute of Utah, University of Utah, Salt Lake City, Utah 84108, USA.
ACS Nano. 2011 Jul 26;5(7):5717-28. doi: 10.1021/nn2013904. Epub 2011 Jun 8.
Understanding the toxicity of silica nanoparticles (SiO(2)) on the cellular level is crucial for rational design of these nanomaterials for biomedical applications. Herein, we explore the impacts of geometry, porosity, and surface charge of SiO(2) on cellular toxicity and hemolytic activity. Nonporous Stöber silica nanospheres (115 nm diameter), mesoporous silica nanospheres (120 nm diameter, aspect ratio 1), mesoporous silica nanorods with aspect ratio of 2, 4, and 8 (width by length 80 × 200 nm, 150 × 600 nm, 130 × 1000 nm), and their cationic counterparts were evaluated on macrophages, lung carcinoma cells, and human erythrocytes. It was shown that the toxicity of SiO(2) is cell-type dependent and that surface charge and pore size govern cellular toxicity. Using inductively coupled plasma mass spectrometry, the cellular association of SiO(2) was quantitated with the association amount increasing in the following order: mesoporous SiO(2) (aspect ratio 1, 2, 4, 8) < amine-modified mesoporous SiO(2) (aspect ratio 1, 2, 4, 8) < amine-modified nonporous Stöber SiO(2) < nonporous Stöber SiO(2). Geometry did not seem to influence the extent of SiO(2) association at early or extended time points. The level of cellular association of the nanoparticles was directly linked to the extent of plasma membrane damage, suggesting a biological cause-and-effect relationship. Hemolysis assay showed that the hemolytic activity was porosity- and geometry-dependent for bare SiO(2) and surface-charge-dependent for amine-modified SiO(2). A good correlation between hemolytic activity and cellular association was found on a similar dosage basis. These results can provide useful guidelines for the rational design of SiO(2) in nanomedicine.
了解硅纳米粒子（SiO(2)）在细胞水平上的毒性对于这些纳米材料在生物医学应用中的合理设计至关重要。在此，我们探索了 SiO(2)的几何形状、多孔性和表面电荷对细胞毒性和溶血活性的影响。非多孔 Stöber 硅纳米球（直径 115nm）、介孔硅纳米球（直径 120nm，纵横比 1）、纵横比为 2、4 和 8 的介孔硅纳米棒（80×200nm、150×600nm、130×1000nm）及其阳离子对应物在巨噬细胞、肺癌细胞和人红细胞上进行了评估。结果表明，SiO(2)的毒性具有细胞类型依赖性，表面电荷和孔径大小决定了细胞毒性。使用电感耦合等离子体质谱法，定量测定了 SiO(2)与细胞的结合量，结合量按以下顺序增加：介孔 SiO(2)（纵横比 1、2、4、8）<胺改性介孔 SiO(2)（纵横比 1、2、4、8）<胺改性非多孔 Stöber SiO(2)<非多孔 Stöber SiO(2)。在早期或延长时间点，几何形状似乎不影响 SiO(2)与细胞的结合程度。纳米颗粒与细胞的结合程度直接与质膜损伤程度相关，这表明存在生物学的因果关系。溶血试验表明，裸 SiO(2)的溶血活性与多孔性和几何形状有关，而胺改性 SiO(2)的溶血活性与表面电荷有关。在相似剂量基础上，发现溶血活性与细胞结合之间存在良好的相关性。这些结果可为纳米医学中 SiO(2)的合理设计提供有用的指导。
