In recent years there has been considerable effort to understand the interaction of nanomaterials with the skin. In this study we use an in vivo mouse model of allergic contact dermatitis to investigate how nanoparticles (NPs) may alter allergic responses in skin. We investigate a variety of NPs that vary in size, charge and composition. Results show that small (<200 nm) negative and neutral charged NPs exhibit an immunosuppressive effect but that positively charged NPs do not. Confocal imaging suggests positively charged NPs may penetrate skin to a lesser extent and thereby are less able interact with and alter the local immune responses. Interestingly, negatively charged silica (20 nm) NPs suppress allergic response to two chemically distinct sensitizers; 1-fluoro-2, 4-dinitrobenzene and 2-deoxyurushiol. Skin wiping and NP application time studies suggest that the immunomodulatory mechanism is not due solely to the blocking of sensitizer adduct formation in skin. Results suggest that NPs modulate early immune events that impact mast cell degranulation. Our study shows for the first time the potential to modulate the elicitation phase of the allergic response which depends on the NP charge and composition. These finding can be used to inform the design topical therapeutics to mitigate allergic responses in skin.

BackgroundThe effects of carbon nanotubes on skin toxicity have not been extensively studied; however, our lab has previously shown that a carboxylated multi-walled carbon nanotube (MWCNT) exacerbates the 2, 4-dinitrofluorobenzene induced contact hypersensitivity response in mice. Here we examine the role of carboxylation in MWCNT skin toxicity.ResultsMWCNTs were analyzed by transmission electron microscopy, zetasizer, and x-ray photoelectron spectroscopy to fully characterize the physical properties. Two MWCNTs with different levels of surface carboxylation were chosen for further testing. The MWCNTs with a high level of carboxylation displayed increased cytotoxicity in a HaCaT keratinocyte cell line, compared to the MWCNTs with intermediate levels of carboxylation. However, neither functionalized MWCNT increased the level of in vitro reactive oxygen species suggesting an alternative mechanism of cytotoxicity. Each MWCNT was tested in the contact hypersensitivity model, and only the MWCNTs with greater than 20% surface carboxylation exacerbated the ear swelling responses. Analysis of the skin after MWCNT exposure reveals that the same MWCNTs with a high level of carboxylation increase epidermal thickness, mast cell and basophil degranulation, and lead to increases in polymorphonuclear cell recruitment when co-administered with 2, 4-dinitrofluorobenzene.ConclusionsThe data presented here suggest that acute, topical application of low doses of MWCNTs can induce keratinocyte cytotoxicity and exacerbation of allergic skin conditions in a carboxylation dependent manner.Electronic supplementary materialThe online version of this article (10.1186/s12989-018-0285-x) contains supplementary material, which is available to authorized users.

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.

BackgroundPrevious work has demonstrated size, surface charge and skin barrier dependent penetration of nanoparticles into the viable layers of mouse skin. The goal of this work was to characterize the tissue distribution and mechanism of transport of nanoparticles beyond skin, with and without Ultraviolet Radiation (UVR) induced skin barrier disruption. Atomic absorption spectroscopy (AAS), flow cytometry and confocal microscopy were used to examine the effect of UVR dose (180 and 360 mJ/cm2 UVB) on the skin penetration and systemic distribution of quantum dot (QD) nanoparticles topically applied at different time-points post UVR using a hairless C57BL/6 mouse model.ResultsResults indicate that QDs can penetrate mouse skin, regardless of UVR exposure, as evidenced by the increased cadmium in the local lymph nodes of all QD treated mice. The average % recovery for all treatment groups was 69.68% with ~66.84% of the applied dose recovered from the skin (both epicutaneous and intracutaneous). An average of 0.024% of the applied dose was recovered from the lymph nodes across various treatment groups. When QDs are applied 4 days post UV irradiation, at the peak of the skin barrier defect and LC migration to the local lymph node, there is an increased cellular presence of QD in the lymph node; however, AAS analysis of local lymph nodes display no difference in cadmium levels due to UVR treatment.ConclusionsOur data suggests that Langerhans cells (LCs) can engulf QDs in skin, but transport to the lymph node may occur by both cellular (dendritic and macrophage) and non-cellular mechanisms. It is interesting that these specific nanoparticles were retained in skin similarly regardless of UVR barrier disruption, but the observed skin immune cell interaction with nanoparticles suggest a potential for immunomodulation, which we are currently examining in a murine model of skin allergy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-017-0191-7) contains supplementary material, which is available to authorized users.

Ultraviolet radiation (UVR) is a consistent part of the environment that has both beneficial and harmful effects on human health. UVR filters in the form of commercial sunscreens have been widely used to reduce the negative health effects of UVR exposure. Despite their benefit, literature suggests that some filters can penetrate skin and have off-target biological effects. We noted that many organic filters are hydrophobic and contain aromatic rings, making them potential modulators of Aryl hydrocarbon receptor (AhR) signaling. We hypothesized that some filters may be able to act as agonists or antagonists on the AhR. Using a luciferase reporter cell line, we observed that the UVR filter octinoxate potentiated the ability of the known AhR ligand, 6-formylindolo[3,2-b]carbazole (FICZ), to activate the AhR. Co-treatments of keratinocytes with octinoxate and FICZ lead to increased levels of cytochrome P4501A1 (CYP1A1) and P4501B1 (CYP1B1) mRNA transcripts, in an AhR dependent fashion. Mechanistic studies revealed that octinoxate is an inhibitor of CYP1A1 and CYP1B1, with IC50 values at approximately 1 µM and 586 nM, respectively. In vivo topical application of octinoxate and FICZ also elevated CYP1A1 and CYP1B1 mRNA levels in mouse skin. Our results show that octinoxate is able to indirectly modulate AhR signaling by inhibiting CYP1A1 and CYP1B1 enzyme function, which may have important downstream consequences for the metabolism of various compounds and skin integrity. It is important to continue studying the off-target effects of octinoxate and other UVR filters, since they are used on skin on a daily basis world-wide.