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Protein corona changes mediated by surface modification of amorphous silica nanoparticles suppress acute toxicity and activation of intrinsic coagulation cascade in mice

机译:由无定形二氧化硅纳米粒子的表面修饰介导的蛋白质电晕变化抑制小鼠的急性毒性和内在凝血级联反应的激活

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摘要

Recently, nanomaterial-mediated biological effects have been shown to be governed by the interaction of nanomaterials with some kinds of proteins in biological fluids, and the physical characteristics of the nanomaterials determine the extent and type of their interactions with proteins. Here, we examined the relationships between the surface properties of amorphous silica nanoparticles with diameters of 70 nm (nSP70), their interactions with some proteins in biological fluids, and their toxicity in mice after intravenous administration. The surface modification of nSP70 with amino groups (nSP70-N) prevented acute lethality and abnormal activation of the coagulation cascade found in the nSP70-treated group of mice. Since our previous study showed that coagulation factor XII played a role in the nSP70-mediated abnormal activation of the coagulation cascade, we examined the interaction of nSP70 and nSP70-N with coagulation factor XII. Coagulation factor XII bonded to the surface of nSP70 to a greater extent than that observed for nSP70-N, and consequently more activation of coagulation factor XII was observed for nSP70 than for nSP70-N. Collectively, our results suggest that controlling the interaction of nSP70 with blood coagulation factor XII by modifying the surface properties would help to inhibit the nSP70-mediated abnormal activation of the blood coagulation cascade.
机译:近来,已经证明纳米材料介导的生物效应受纳米材料与生物流体中某些蛋白质的相互作用支配,并且纳米材料的物理特性决定了它们与蛋白质相互作用的程度和类型。在这里,我们检查了直径为70 nm的无定形二氧化硅纳米粒子(nSP70)的表面性质,它们与生物液体中某些蛋白质的相互作用以及静脉内给药后对小鼠的毒性之间的关系。 nSP70的氨基表面修饰(nSP70-N)防止了急性致死性和在nSP70处理组的小鼠中发现的凝血级联反应的异常激活。由于我们先前的研究表明凝血因子XII在nSP70介导的凝血级联的异常激活中起作用,因此我们检查了nSP70和nSP70-N与凝血因子XII的相互作用。与nSP70-N相比,凝血因子XII结合到nSP70的表面的程度更大,因此与nSP70-N相比,nSP70观察到更多的凝血因子XII活化。总的来说,我们的结果表明通过改变表面性质来控制nSP70与凝血因子XII的相互作用将有助于抑制nSP70介导的凝血级联的异常激活。

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