Silver nanoparticles (AgNPs) are among the most commercialized nanomaterials in biomedicine due to their antimicrobial and anti-inflammatory properties. Nevertheless, possible health hazards of exposure to AgNPs are yet to be understood and therefore raise public concern in regards of their safety.

In this study, sex-related differences, role of steroidal hormones and influence of two different surface stabilizing agents (polymer vs. protein) on distribution and adverse effects of AgNPs were investigated in vivo. Intact and gonadectomised male and female mice were treated with seven AgNPs doses administered intraperitoneally during 21 days. After treatment, steroid hormone levels in serum, accumulation of Ag levels and oxidative stress biomarkers in liver, kidneys, brain and lungs were determined.

Sex-related differences were observed in almost all tissues. Concentration of Ag was significantly higher in the liver of females compared to males. No significant difference was found for AgNP accumulation in lungs between females and males, while the lungs of intact males showed significantly higher Ag accumulation compared to gonadectomised group. Effect of surface coating was also observed, as Ag accumulation was significantly higher in kidneys and liver of intact females, as well as in kidneys and brain of intact males treated with protein-coated AgNPs compared to polymeric AgNPs. Oxidative stress response to AgNPs was the most pronounced in kidneys where protein-coated AgNPs induced stronger effects compared to polymeric AgNPs. Interestingly, protein-coated AgNPs reduced generation of reactive oxygen species in brains of females and gonadectomised males. Although there were no significant differences in levels of hormones in the AgNP-exposed animals compared to controls, sex-related differences in oxidative stress parameters were observed in all organs.

Results of this study highlight the importance of including the sex-related differences and effects of protein corona in biosafety evaluation of AgNPs exposure.

银纳米粒子 (AgNPs) 因其抗菌和抗炎特性而成为生物医学中商业化程度最高的纳米材料之一。然而，接触 AgNPs 可能对健康造成的危害尚待了解，因此引起了公众对其安全性的关注。

在这项研究中，在体内研究了性别相关差异、甾体激素的作用以及两种不同表面稳定剂（聚合物与蛋白质）对 AgNPs 分布和不利影响的影响。在 21 天内，用 7 剂 AgNPs 腹膜内给药对完整和切除性腺的雄性和雌性小鼠进行治疗。治疗后，测定血清中的类固醇激素水平、肝、肾、脑和肺中Ag水平和氧化应激生物标志物的积累。

在几乎所有组织中都观察到与性别有关的差异。与男性相比，女性肝脏中的Ag浓度显着更高。女性和男性的肺中 AgNP 积累没有显着差异，而与去性腺切除组相比，完整男性的肺中 Ag 积累显着更高。还观察到表面涂层的影响，因为与聚合 AgNPs 相比，完整女性的肾脏和肝脏中的 Ag 积累显着更高，以及用蛋白质包被的 AgNPs 处理的完整男性的肾脏和大脑中的 Ag 积累显着更高。与聚合 AgNPs 相比，对 AgNPs 的氧化应激反应在肾脏中最为明显，其中蛋白质包被的 AgNPs 诱导更强的作用。有趣的是，蛋白质包被的 AgNPs 减少了女性和切除性腺的男性大脑中活性氧的产生。尽管与对照组相比，AgNP 暴露动物的激素水平没有显着差异，但在所有器官中都观察到了与性别相关的氧化应激参数差异。

这项研究的结果强调了在 AgNPs 暴露的生物安全评估中包括与性别相关的差异和蛋白质电晕的影响的重要性。