Abstract
Amorphous silicon dioxide nanoparticles (SiNPs) are ubiquitous, and they are currently found in cosmetics, drugs, and foods. Biomedical research is also focused on using these nanoparticles as drug delivery and bio-sensing platforms. Due to the high potential for skin exposure to SiNPs, research into the effect of topical exposure on both healthy and inflammatory skin models is warranted. While we observe only minimal effects of SiNPs on healthy mouse skin, there is an immunomodulatory effect of these NPs in a model of allergic contact dermatitis. The effect appears to be mediated partly by keratinocytes and results in decreases in epidermal hyperplasia, inflammatory cytokine release, immune cell infiltration, and a subsequent reduction in skin swelling. Additional research is required to further our mechanistic understanding and to validate the extent of this immunomodulatory effect in human subjects in order to assess the potential prophylactic use of SiNPs for treating allergic skin conditions.
Highlights
Amorphous silicon dioxide particles are typically produced via the Stöber or microemulsion method[1,2]
Since a number of immunomodulatory cytokines are known to be produced by keratinocytes, we examined interleukin 6 (IL-6) and IL-8 released by the HaCaT cells exposed to DNFB and 20 nm SiNP (0, 0.5 and 5 ug/mL)
Based on our previous work[32], it seemed that decreased mast cell degranulation would have a larger role in SiNP induced skin immunosuppression; we observed only minimal mast cell degranulation at 24 hours, even in the DNFB only treatments, that alone do not explain the differences in ear swelling
Summary
Amorphous silicon dioxide particles are typically produced via the Stöber or microemulsion method[1,2]. Due to the perceived safety and the wide array of surface and structural modifications available, SiNPs are currently the subject of several studies examining potential uses for drug delivery[6,7,8], bio-sensing[9], and vaccination[10,11,12,13] Both the increased use of SiNPs in cosmetics and the new research utilizing these NPs as transdermal drug delivery agents will lead to increased dermal exposure to SiNPs. While there are numerous studies examining the in vivo toxicity of high dose, acute exposures to amorphous SiNPs on the lungs[14,15,16,17] and gastrointestinal tracts[18,19] of rodents, there are relatively few studies examining the dermal toxicity of these NPs. Early studies of SiNP dermal toxicity revealed dose dependent cytotoxicity of in vitro keratinocytes and Langerhan’s cells[20,21], associated with increases in reactive oxygen species (ROS) generation. We examine the histology, inflammatory cytokine expression, and immune cell infiltration in the skin of mice exposed to DNFB and SiNPs, to further characterize the immunosuppressive effects
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