Dutta Debamitra, Sundaram Shanmugavelayutham Kamakshi, Teeguarden Justin Gary, Riley Brian Joseph, Fifield Leonard Sheldon, Jacobs Jon Morrell, Addleman Shane Raymond, Kaysen George Alan, Moudgil Brij Mohan, Weber Thomas Joseph
Particle Engineering Research Center and the Department of Materials Science and Engineering, University of Florida, Gainesville, Florida 32611, USA.
Toxicol Sci. 2007 Nov;100(1):303-15. doi: 10.1093/toxsci/kfm217. Epub 2007 Aug 19.
The possible combination of specific physicochemical properties operating at unique sites of action within cells and tissues has led to considerable uncertainty surrounding nanomaterial toxic potential. We have investigated the importance of proteins adsorbed onto the surface of two distinct classes of nanomaterials (single-walled carbon nanotubes [SWCNTs]; 10-nm amorphous silica) in guiding nanomaterial uptake or toxicity in the RAW 264.7 macrophage-like model. Albumin was identified as the major fetal bovine or human serum/plasma protein adsorbed onto SWCNTs, while a distinct protein adsorption profile was observed when plasma from the Nagase analbuminemic rat was used. Damaged or structurally altered albumin is rapidly cleared from systemic circulation by scavenger receptors. We observed that SWCNTs inhibited the induction of cyclooxygenase-2 (Cox-2) by lipopolysaccharide (LPS; 1 ng/ml, 6 h) and this anti-inflammatory response was inhibited by fucoidan (scavenger receptor antagonist). Fucoidan also reduced the uptake of fluorescent SWCNTs (Alexa647). Precoating SWCNTs with a nonionic surfactant (Pluronic F127) inhibited albumin adsorption and anti-inflammatory properties. Albumin-coated SWCNTs reduced LPS-mediated Cox-2 induction under serum-free conditions. SWCNTs did not reduce binding of LPS(Alexa488) to RAW 264.7 cells. The profile of proteins adsorbed onto amorphous silica particles (50-1000 nm) was qualitatively different, relative to SWCNTs, and precoating amorphous silica with Pluronic F127 dramatically reduced the adsorption of serum proteins and toxicity. Collectively, these observations suggest an important role for adsorbed proteins in modulating the uptake and toxicity of SWCNTs and nano-sized amorphous silica.
在细胞和组织内独特作用位点发挥作用的特定物理化学性质的可能组合，导致围绕纳米材料潜在毒性存在相当大的不确定性。我们研究了吸附在两类不同纳米材料（单壁碳纳米管[SWCNTs]；10纳米无定形二氧化硅）表面的蛋白质在RAW 264.7巨噬细胞样模型中引导纳米材料摄取或毒性方面的重要性。白蛋白被确定为吸附在SWCNTs上的主要胎牛或人血清/血浆蛋白，而使用长濑无白蛋白血症大鼠的血浆时观察到明显不同的蛋白质吸附谱。受损或结构改变的白蛋白会被清道夫受体迅速从体循环中清除。我们观察到SWCNTs抑制脂多糖（LPS；1纳克/毫升，6小时）诱导的环氧化酶-2（Cox-2），而这种抗炎反应被岩藻依聚糖（清道夫受体拮抗剂）抑制。岩藻依聚糖还减少了荧光SWCNTs（Alexa647）的摄取。用非离子表面活性剂（普朗尼克F127）预包被SWCNTs可抑制白蛋白吸附和抗炎特性。在无血清条件下，白蛋白包被的SWCNTs降低了LPS介导的Cox-2诱导。SWCNTs没有降低LPS（Alexa488）与RAW 264.7细胞的结合。相对于SWCNTs，吸附在无定形二氧化硅颗粒（50 - 1000纳米）上的蛋白质谱在质量上有所不同，用普朗尼克F127预包被无定形二氧化硅可显著降低血清蛋白吸附和毒性。总体而言，这些观察结果表明吸附的蛋白质在调节SWCNTs和纳米尺寸无定形二氧化硅的摄取和毒性方面具有重要作用。
