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Immunotoxicity of silicon dioxide nanoparticles with different sizes and electrostatic charge.

Kim JH, Kim CS, Ignacio RM, Kim DH, Sajo ME, Maeng EH, Qi XF, Park SE, Kim YR, Kim MK, Lee KJ, Kim SK - Int J Nanomedicine (2014)

Bottom Line: However, little is known about the biological effects and potential hazards of SiO2.Specifically, the SiO2 (EN20(-)) NPs showed the most pronounced reduction.Both the size and charge of SiO2 using murine macrophage RAW 264.7 cells decreased cell viability dose-dependently.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Effect of differently sized and electrostatic charged SiO2 NPs on the viability of murine macrophage RAW 264.7 cells.Notes: Cells were incubated with indicated concentrations of colloidal SiO2 NPs: (A) SiO2EN20(−); (B) SiO2EN100(−); (C) SiO2EN20(R); and (D) SiO2N100(R) for 24 hours. Cells not treated with SiO2 NPs served as the control in the experiment. A commercially available cell viability assay Cell Counting Kit-8 was used to evaluate the cytotoxicity effect of the SiO2 NPs according to manufacturer’s instructions (Dojindo Molecular Technologies, Inc., Rockville, MD, USA). Data are presented as the mean ± standard deviation. *P<0.05; **P<0.01; ***P<0.001 versus control (0 μg/mL).Abbreviations: SiO2EN(−), negatively charged silicon dioxide; SiO2EN(R), silicon dioxide modified with L-arginine; SiO2, silicon dioxide; NPs, nanoparticles.
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f1-ijn-9-183: Effect of differently sized and electrostatic charged SiO2 NPs on the viability of murine macrophage RAW 264.7 cells.Notes: Cells were incubated with indicated concentrations of colloidal SiO2 NPs: (A) SiO2EN20(−); (B) SiO2EN100(−); (C) SiO2EN20(R); and (D) SiO2N100(R) for 24 hours. Cells not treated with SiO2 NPs served as the control in the experiment. A commercially available cell viability assay Cell Counting Kit-8 was used to evaluate the cytotoxicity effect of the SiO2 NPs according to manufacturer’s instructions (Dojindo Molecular Technologies, Inc., Rockville, MD, USA). Data are presented as the mean ± standard deviation. *P<0.05; **P<0.01; ***P<0.001 versus control (0 μg/mL).Abbreviations: SiO2EN(−), negatively charged silicon dioxide; SiO2EN(R), silicon dioxide modified with L-arginine; SiO2, silicon dioxide; NPs, nanoparticles.

Mentions: After exposure for 24 hours at varying doses of SiO2, murine macrophage RAW 264.7 cell viability detected by the CCK-8 assay resulted in an explicit dose-dependent reduction (Figure 1). Also, size- and electrostatic charge-dependent cytotoxicity of SiO2 NPs were found. The EC50 values after 24 hours of exposure were 71.10 ug/mL (SiO2EN20[−]), 211.4 ug/mL (SiO2EN100[−]), 233.2 ug/mL (SiO2EN20[R]), and 833.6 ug/mL (SiO2EN100[R]).


Immunotoxicity of silicon dioxide nanoparticles with different sizes and electrostatic charge.

Kim JH, Kim CS, Ignacio RM, Kim DH, Sajo ME, Maeng EH, Qi XF, Park SE, Kim YR, Kim MK, Lee KJ, Kim SK - Int J Nanomedicine (2014)

Effect of differently sized and electrostatic charged SiO2 NPs on the viability of murine macrophage RAW 264.7 cells.Notes: Cells were incubated with indicated concentrations of colloidal SiO2 NPs: (A) SiO2EN20(−); (B) SiO2EN100(−); (C) SiO2EN20(R); and (D) SiO2N100(R) for 24 hours. Cells not treated with SiO2 NPs served as the control in the experiment. A commercially available cell viability assay Cell Counting Kit-8 was used to evaluate the cytotoxicity effect of the SiO2 NPs according to manufacturer’s instructions (Dojindo Molecular Technologies, Inc., Rockville, MD, USA). Data are presented as the mean ± standard deviation. *P<0.05; **P<0.01; ***P<0.001 versus control (0 μg/mL).Abbreviations: SiO2EN(−), negatively charged silicon dioxide; SiO2EN(R), silicon dioxide modified with L-arginine; SiO2, silicon dioxide; NPs, nanoparticles.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4279855&req=5

f1-ijn-9-183: Effect of differently sized and electrostatic charged SiO2 NPs on the viability of murine macrophage RAW 264.7 cells.Notes: Cells were incubated with indicated concentrations of colloidal SiO2 NPs: (A) SiO2EN20(−); (B) SiO2EN100(−); (C) SiO2EN20(R); and (D) SiO2N100(R) for 24 hours. Cells not treated with SiO2 NPs served as the control in the experiment. A commercially available cell viability assay Cell Counting Kit-8 was used to evaluate the cytotoxicity effect of the SiO2 NPs according to manufacturer’s instructions (Dojindo Molecular Technologies, Inc., Rockville, MD, USA). Data are presented as the mean ± standard deviation. *P<0.05; **P<0.01; ***P<0.001 versus control (0 μg/mL).Abbreviations: SiO2EN(−), negatively charged silicon dioxide; SiO2EN(R), silicon dioxide modified with L-arginine; SiO2, silicon dioxide; NPs, nanoparticles.
Mentions: After exposure for 24 hours at varying doses of SiO2, murine macrophage RAW 264.7 cell viability detected by the CCK-8 assay resulted in an explicit dose-dependent reduction (Figure 1). Also, size- and electrostatic charge-dependent cytotoxicity of SiO2 NPs were found. The EC50 values after 24 hours of exposure were 71.10 ug/mL (SiO2EN20[−]), 211.4 ug/mL (SiO2EN100[−]), 233.2 ug/mL (SiO2EN20[R]), and 833.6 ug/mL (SiO2EN100[R]).

Bottom Line: However, little is known about the biological effects and potential hazards of SiO2.Specifically, the SiO2 (EN20(-)) NPs showed the most pronounced reduction.Both the size and charge of SiO2 using murine macrophage RAW 264.7 cells decreased cell viability dose-dependently.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus