Evaluation of the skin sensitizing potential of gold nanoparticles and the impact of established dermal sensitivity on the pulmonary immune response to various forms of gold

Abstract

Abstract Gold compounds are associated with diverse immune effects, including allergy. Whether gold nanoparticles (AuNP) cause similar effects remains unknown. To address this, three in vivo studies were performed. AuNP (29nm)dermal sensitization potential was assessed via Local Lymph Node Assay (LLNA) along with soluble gold salts (AuCl3) and larger particles (Au, 942nm). AuCl3 caused lymph node (LN) expansion (SI 10.9), whereas Au and AuNP did not, indicating minimal potential for dermal sensitization. Next, pulmonary immune effects of AuNP (10μg, 30μg, 90μg) were assessed 1d, 4d, 8d post-aspiration. AuNP had no effect on lung injury or inflammation, but did increase LN CD4+ T- and B-cells by 4d. Finally, mice were dermally sensitized to AuCl3 (d1-3), then aspirated 1× (d10),2× (d10, 14), or 3× (d10, 14, 18) with Au or AuNP in doses normalized for mass or surface area (SA), to assess impact of existing contact sensitivity on lung immune responses. In dermally sensitized groups, increased BAL lymphocytes were seen after two and three aspirations, which correlated to the administered SA. The highest AuNP dose caused the greatest increase in total BAL lymphocytes, as well as increased number, proportion, and activation of BAL/LN CD8+ T-cells. Comparatively, the lower SA-based doses of Au/AuNP resulted in elevated numbers of BAL T-cells(predominantly CD4+ phenotype), exposure-dependent increases in serum IgE, and selective expansion/activation of LN CD4+ T- and B-cells, suggestive of a Th2-polarized state. Overall, these findings suggest that AuNP are not likely to cause allergic sensitization; however, established contact sensitivity to gold may be associated with increased immune reactivity to AuNP following respiratory exposure.