Immunomodulatory Effects of Nanoparticles on Skin Allergy

Abstract

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.

Multi-walled carbon nanotube oxidation dependent keratinocyte cytotoxicity and skin inflammation

“…The in vitro data is suggestive of potential MWCNT induced dermal irritation, and to examine the effect of these MWCNTs on normal and inflamed skin, our lab uses hairless C57BL/6 mice treated with either vehicle or a DNFB sensitizer. As we have previously reported, topically applied MWCNT High-COOH particles exacerbate the DNFB induced CHS ear swelling response 24 h after co-challenge with 0.2% DNFB and 1 μg/ear MWCNT High-COOH [34]. This response appears to be synergistic as the MWCNT High-COOH particles have no effect on ear swelling without the sensitizer (Fig.…”

“…We previously reported that the exacerbation of CHS induced ear swelling caused by the MWCNT High-COOH was associated with increased mast cell degranulation [34]. Here we examined the levels of both mast cell and basophil degranulation by counting the number of degranulating and intact cells in toluidine blue stained skin sections.…”

“…This model is preferable, since topical treatments would necessitate hair removal in other mouse models, and shaving or depilatory agents can cause unwanted skin barrier defects. The mice examined were all male and between 5 and 6 months old, since we have identified age, but not sex-based differences in the DNFB induced CHS response of these mice [34]. The mice were housed individually in standard cages to prevent interactions that would damage the skin or lead to cross contamination of topical agents.…”

“…Due to the increasing prevalence of allergic skin disorders such as atopic dermatitis and allergic contact dermatitis [32, 33], it is important to examine the toxicity of CNTs in both healthy and disease models. Recently, our lab reported that a relatively low dose of 1 μg/ear of carboxylated MWCNT could significantly augment the 2,4-dinitrofluorobenzene (DNFB) induced contact hypersensitivity (CHS) response in a hairless C57BL/6 mouse model, and this response was associated with an increase in mast cell degranulation [34].…”

Nanotechnology-Based Vaccines for Allergen-Specific Immunotherapy: Potentials and Challenges of Conventional and Novel Adjuvants under Research

“…In addition to the size, the surface charge, chemical composition, shape and solubility makes them attractive for AIT. Jatana et al determined the influence of size and charge of different nanoparticles (gold, silver, silica, and titanium dioxide) on immunomodulation in a mouse model of allergic contact dermatitis and concluded that small and negatively charged nanoparticles exhibited immunosuppressive effects [82]. Biodegradable polymeric nanoparticles that are biocompatible with tissues and cells, can be promising candidates in AIT that might reduce the unwanted side effects associated with the current therapy, using alum as adjuvant.…”