Kim Jae-Hyun, Kim Cheol-Su, Ignacio Rosa Mistica Coles, Kim Dong-Heui, Sajo Ma Easter Joy, Maeng Eun Ho, Qi Xu-Feng, Park Seong-Eun, Kim Yu-Ri, Kim Meyoung-Kon, Lee Kyu-Jae, Kim Soo-Ki
Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea.
Department of Environmental Medical Biology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea.
Int J Nanomedicine. 2014 Dec 15;9 Suppl 2(Suppl 2):183-93. doi: 10.2147/IJN.S57934. eCollection 2014.
Silicon dioxide (SiO2) nanoparticles (NPs) have been widely used in the biomedical field, such as in drug delivery and gene therapy. However, little is known about the biological effects and potential hazards of SiO2. Herein, the colloidal SiO2 NPs with two different sizes (20 nm and 100 nm) and different charges (L-arginine modified: SiO2 (EN20[R]), SiO2 (EN100[R]); and negative: SiO2 (EN20[-]), SiO2 (EN100[-]) were orally administered (750 mg/kg/day) in female C57BL/6 mice for 14 days. Assessments of immunotoxicity include hematology profiling, reactive oxygen species generation and their antioxidant effect, stimulation assays for B- and T-lymphocytes, the activity of natural killer (NK) cells, and cytokine profiling. In vitro toxicity was also investigated in the RAW 264.7 cell line. When the cellularity of mouse spleen was evaluated, there was an overall decrease in the proliferation of B- and T-cells for all the groups fed with SiO2 NPs. Specifically, the SiO2 (EN20(-)) NPs showed the most pronounced reduction. In addition, the nitric oxide production and NK cell activity in SiO2 NP-fed mice were significantly suppressed. Moreover, there was a decrease in the serum concentration of inflammatory cytokines such as interleukin (IL)-1β, IL-12 (p70), IL-6, tumor necrosis factor-α, and interferon-γ. To elucidate the cytotoxicity mechanism of SiO2 in vivo, an in vitro study using the RAW 264.7 cell line was performed. Both the size and charge of SiO2 using murine macrophage RAW 264.7 cells decreased cell viability dose-dependently. Collectively, our data indicate that different sized and charged SiO2 NPs would cause differential immunotoxicity. Interestingly, the small-sized and negatively charged SiO2 NPs showed the most potent in vivo immunotoxicity by way of suppressing the proliferation of lymphocytes, depressing the killing activity of NK cells, and decreasing proinflammatory cytokine production, thus leading to immunosuppression.
二氧化硅（SiO₂）纳米颗粒（NPs）已广泛应用于生物医学领域，如药物递送和基因治疗。然而，人们对SiO₂的生物学效应和潜在危害知之甚少。在此，将两种不同尺寸（20纳米和100纳米）和不同电荷（L-精氨酸修饰：SiO₂（EN20[R]）、SiO₂（EN100[R]）；以及阴性：SiO₂（EN20[-]）、SiO₂（EN100[-]））的胶体SiO₂ NPs以750毫克/千克/天的剂量口服给予雌性C57BL/6小鼠，持续14天。免疫毒性评估包括血液学分析、活性氧生成及其抗氧化作用、B淋巴细胞和T淋巴细胞刺激试验、自然杀伤（NK）细胞活性以及细胞因子分析。还在RAW 264.7细胞系中研究了体外毒性。当评估小鼠脾脏细胞数量时，所有喂食SiO₂ NPs的组中B细胞和T细胞的增殖总体下降。具体而言，SiO₂（EN20(-)）NPs表现出最明显的减少。此外，喂食SiO₂ NPs的小鼠体内一氧化氮生成和NK细胞活性受到显著抑制。此外，炎症细胞因子如白细胞介素（IL）-1β、IL-12（p70）、IL-6、肿瘤坏死因子-α和干扰素-γ的血清浓度降低。为了阐明SiO₂在体内的细胞毒性机制，使用RAW 264.7细胞系进行了体外研究。使用小鼠巨噬细胞RAW 264.7细胞时，SiO₂的尺寸和电荷均剂量依赖性地降低细胞活力。总体而言，我们的数据表明不同尺寸和电荷的SiO₂ NPs会导致不同的免疫毒性。有趣的是，小尺寸且带负电荷的SiO₂ NPs通过抑制淋巴细胞增殖、降低NK细胞杀伤活性和减少促炎细胞因子产生，在体内表现出最强大的免疫毒性，从而导致免疫抑制。
