Chen Yu-Shiun, Hung Yao-Ching, Liau Ian, Huang G Steve
Nanoscale Res Lett. 2009 May 8;4(8):858-864. doi: 10.1007/s11671-009-9334-6.
The environmental impact of nanoparticles is evident; however, their toxicity due to their nanosize is rarely discussed. Gold nanoparticles (GNPs) may serve as a promising model to address the size-dependent biological response to nanoparticles because they show good biocompatibility and their size can be controlled with great precision during their chemical synthesis. Naked GNPs ranging from 3 to 100 nm were injected intraperitoneally into BALB/C mice at a dose of 8 mg/kg/week. GNPs of 3, 5, 50, and 100 nm did not show harmful effects; however, GNPs ranging from 8 to 37 nm induced severe sickness in mice. Mice injected with GNPs in this range showed fatigue, loss of appetite, change of fur color, and weight loss. Starting from day 14, mice in this group exhibited a camel-like back and crooked spine. The majority of mice in these groups died within 21 days. Injection of 5 and 3 nm GNPs, however, did not induce sickness or lethality in mice. Pathological examination of the major organs of the mice in the diseased groups indicated an increase of Kupffer cells in the liver, loss of structural integrity in the lungs, and diffusion of white pulp in the spleen. The pathological abnormality was associated with the presence of gold particles at the diseased sites, which were verified by ex vivo Coherent anti-Stoke Raman scattering microscopy. Modifying the surface of the GNPs by incorporating immunogenic peptides ameliorated their toxicity. This reduction in the toxicity is associated with an increase in the ability to induce antibody response. The toxicity of GNPs may be a fundamental determinant of the environmental toxicity of nanoparticles.
纳米颗粒对环境的影响是显而易见的；然而，因其纳米尺寸所导致的毒性却鲜有讨论。金纳米颗粒（GNPs）可能是一个很有前景的模型，可用于研究纳米颗粒尺寸依赖性的生物反应，因为它们具有良好的生物相容性，并且在化学合成过程中其尺寸能够得到精确控制。将粒径范围为3至100纳米的裸金纳米颗粒以8毫克/千克/周的剂量腹腔注射到BALB/C小鼠体内。3、5、50和100纳米的金纳米颗粒未显示出有害影响；然而，粒径范围为8至37纳米的金纳米颗粒却会致使小鼠患上重病。注射了该粒径范围金纳米颗粒的小鼠出现疲劳、食欲不振、毛色改变和体重减轻的症状。从第14天开始，该组小鼠呈现出骆驼样的背部和脊柱弯曲。这些组中的大多数小鼠在21天内死亡。然而，注射5纳米和3纳米的金纳米颗粒并未导致小鼠患病或死亡。对患病组小鼠主要器官进行的病理检查表明，肝脏中的库普弗细胞增多，肺部结构完整性丧失，脾脏白髓扩散。这种病理异常与患病部位存在金颗粒有关，这已通过离体相干反斯托克斯拉曼散射显微镜得到证实。通过掺入免疫原性肽来修饰金纳米颗粒的表面可减轻其毒性。毒性的降低与诱导抗体反应能力的增强有关。金纳米颗粒的毒性可能是纳米颗粒环境毒性的一个基本决定因素。
