Department of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, USA.
J Am Chem Soc. 2010 Apr 7;132(13):4834-42. doi: 10.1021/ja910846q.
This paper uses the measure of hemolysis to evaluate the toxicity of nonporous and porous silica nanoparticles with varied sizes and investigates the effects of porous structure and integrity on the nanoparticle-cell interaction. The results show that both nonporous and porous silica cause red blood cell membrane damage in a concentration- and size-dependent manner. In the case of mesoporous silica nanoparticles, the size-dependent hemolysis effect is only present when the nanoparticles have long-range ordered porous structure, revealing that pore structure is critical in cell-nanoparticle interactions. Mesoporous silica nanoparticles show lower hemolytic activity than their nonporous counterparts of similar size, likely due to fewer silanol groups on the cell-contactable surface of the porous silica nanoparticles. The extent of hemolysis by mesoporous silica nanoparticles increases as the pore structure is compromised by mild aging in phosphate-buffered solutions, initiating mesopore collapse. The pore integrity of mesoporous silica nanoparticles is examined by TEM, XRD, N(2) adsorption-desorption isotherms, and quantification of dissolved silica. In these nanoparticles, pore stability is clearly an important factor in determining the hemolytic activity; further work demonstrates that nanoparticle-induced hemolysis can be eliminated by modifying the silanol surface with a poly(ethylene glycol) coating.
本文使用溶血测量方法评估了不同尺寸的无孔和多孔硅纳米粒子的毒性，并研究了多孔结构和完整性对纳米粒子与细胞相互作用的影响。结果表明，非多孔和多孔硅均以浓度和尺寸依赖性方式导致红细胞膜损伤。在介孔硅纳米粒子的情况下，只有当纳米粒子具有长程有序的多孔结构时，才会出现尺寸依赖性溶血效应，这表明孔结构在细胞-纳米粒子相互作用中至关重要。介孔硅纳米粒子的溶血活性低于具有相似尺寸的无孔对应物，这可能是由于多孔硅纳米粒子与细胞接触表面上的硅醇基团较少。在磷酸盐缓冲溶液中温和老化会破坏孔结构，从而导致介孔坍塌，介孔硅纳米粒子的溶血程度会随着孔结构的破坏而增加。通过 TEM、XRD、N(2)吸附-解吸等温线和溶解硅的定量分析来检查介孔硅纳米粒子的孔完整性。在这些纳米粒子中，孔稳定性显然是决定溶血活性的重要因素；进一步的工作表明，通过用聚（乙二醇）涂层修饰硅醇表面，可以消除纳米粒子诱导的溶血。
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