Immunotoxicity of silicon dioxide nanoparticles with different size and electrostatic charge

Abstract

Silicon dioxide nanoparticle (SiO2 NP) has been widely used in biomedical field such as drug delivery and gene therapy. However, little is known about the biological effects and potential hazards of SiO2. Herein, the colloidal SiO2NPs with two different sizes (20-NM and 100-NM) and different charge (L-arginine modified: SiO2EN20[R], SiO2EN100[R], and negative: SiO2EN20[-] ,SiO2EN100[-]) were orally administered (750 mg/kg/day) in female C57BL/6 mice for 14 days. Assessments of immunotoxicity include hematology profiling, reactive oxygen species (ROS) generation and antioxidant effect, stimulation assays for B-and T-lymphocytes, the activity of natural killer cells and cytokine profiling. In vitro toxicity was also investigated in RAW 264.7 cell line. When cellularity of mouse spleen was evaluated, overall there is decreased on proliferation of B and T cells for all the groups fed with SiO2 NPs, specifically the SiO2EN20[-] showed the most pronounced reduction. In addition, the NO production and NK cell activity in SiO2 NP-fed mice were significantly suppressed. Moreover, there was decreased in serum concentration of inflammatory cytokines such as interleukin (IL)-1β, IL-12 (p70), IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. To elucidate the cytotoxicity mechanism of SiO2 in in vivo, in vitro study using RAW 264.7 cell line was performed. Both 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 negative charge SiO2NPs showed the most potent in vivo immunotoxicity by way of suppressing the proliferation of lymphocytes, depressing killing activity of NK cell and decreasing the proinflammatory cytokine production, thus, leading to immunosuppression.