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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

The effect on body weight of SiO2 NPs fed to mice.Notes: C57BL/6 mice were treated with varying sizes (20 nm, 100 nm) and charges (SiO2EN[R]; negative, SiO2EN[−]) of 750 mg/kg colloidal SiO2 NPs for 14 days. Body weight was measured all throughout the experiment period, and it served as one of the primary indicators of SiO2 NP immune toxicity. Data are presented as the mean ± standard deviation; n=5.Abbreviations: NC, normal control; SiO2EN(−), negatively charged silicon dioxide; SiO2EN(R), silicon dioxide modified with L-arginine; SiO2, silicon dioxide; NP, nanoparticle; n, number.
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f2-ijn-9-183: The effect on body weight of SiO2 NPs fed to mice.Notes: C57BL/6 mice were treated with varying sizes (20 nm, 100 nm) and charges (SiO2EN[R]; negative, SiO2EN[−]) of 750 mg/kg colloidal SiO2 NPs for 14 days. Body weight was measured all throughout the experiment period, and it served as one of the primary indicators of SiO2 NP immune toxicity. Data are presented as the mean ± standard deviation; n=5.Abbreviations: NC, normal control; SiO2EN(−), negatively charged silicon dioxide; SiO2EN(R), silicon dioxide modified with L-arginine; SiO2, silicon dioxide; NP, nanoparticle; n, number.

Mentions: Body weight gain or loss may indicate an indirect immunotoxic effect. To evaluate the toxicity of SiO2 NPs, mice were fed 750 mg/kg of SiO2 every day for 2 weeks, and their body weight condition was monitored every 5 days for 2 weeks. After 2 weeks of feeding with SiO2 NPs, the groups SiO2EN20(−) and SiO2EN100(R) showed significant elevated body weight (P<0.05) compared to the nontreated group (NC). However, the SiO2EN20(R)-fed group showed significant depressions in body weight (P<0.05) compared to the NC. Further, the SiO2EN100(−)-fed group showed no obvious difference in body weight compared to the NC (Figure 2).


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)

The effect on body weight of SiO2 NPs fed to mice.Notes: C57BL/6 mice were treated with varying sizes (20 nm, 100 nm) and charges (SiO2EN[R]; negative, SiO2EN[−]) of 750 mg/kg colloidal SiO2 NPs for 14 days. Body weight was measured all throughout the experiment period, and it served as one of the primary indicators of SiO2 NP immune toxicity. Data are presented as the mean ± standard deviation; n=5.Abbreviations: NC, normal control; SiO2EN(−), negatively charged silicon dioxide; SiO2EN(R), silicon dioxide modified with L-arginine; SiO2, silicon dioxide; NP, nanoparticle; n, number.
© Copyright Policy
Related In: Results  -  Collection

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

f2-ijn-9-183: The effect on body weight of SiO2 NPs fed to mice.Notes: C57BL/6 mice were treated with varying sizes (20 nm, 100 nm) and charges (SiO2EN[R]; negative, SiO2EN[−]) of 750 mg/kg colloidal SiO2 NPs for 14 days. Body weight was measured all throughout the experiment period, and it served as one of the primary indicators of SiO2 NP immune toxicity. Data are presented as the mean ± standard deviation; n=5.Abbreviations: NC, normal control; SiO2EN(−), negatively charged silicon dioxide; SiO2EN(R), silicon dioxide modified with L-arginine; SiO2, silicon dioxide; NP, nanoparticle; n, number.
Mentions: Body weight gain or loss may indicate an indirect immunotoxic effect. To evaluate the toxicity of SiO2 NPs, mice were fed 750 mg/kg of SiO2 every day for 2 weeks, and their body weight condition was monitored every 5 days for 2 weeks. After 2 weeks of feeding with SiO2 NPs, the groups SiO2EN20(−) and SiO2EN100(R) showed significant elevated body weight (P<0.05) compared to the nontreated group (NC). However, the SiO2EN20(R)-fed group showed significant depressions in body weight (P<0.05) compared to the NC. Further, the SiO2EN100(−)-fed group showed no obvious difference in body weight compared to the NC (Figure 2).

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