Date of Graduation
School of Pharmacy
Many allergenic metals are being manufactured in nanoparticulate forms. Although the decreased size profile of metal nanomaterials has been consistently associated with more pronounced lung toxicity compared to larger materials, it is unclear if metal-induced immunotoxic effects exhibit a similar size-dependency.
The central hypothesis of these studies was that metal nanoparticles cause more pronounced immunomodulatory effects on allergic processes than larger forms of respective metals. Moreover, it was anticipated that, similar to their inflammatory potential in airways, the magnitude of these responses would correlate best with the dose metric of surface area.
The first set of studies utilized fine and ultrafine NiO particles to evaluate respiratory toxicity and augmentation of asthmatic responses with respect to different dose metrics. While the degree of pulmonary inflammation caused by NiO was exclusively associated with the administered surface area, NiO-induced augmentation of OVA allergy appeared dependent on multiple parameters, including particle size and dose mass.
The second set of studies employed gold in bulk and nanoparticulate (AuNP) forms to study allergic sensitization. AuNP exposure did not cause dermal sensitization or notable respiratory immune effects, however, established contact sensitivity to gold conferred notable immune reactivity upon pulmonary AuNP exposure. Subsequent immune responses were directionally-polarized in a surface area-dependent manner, but alterations in several immune markers appeared more closely related to dose mass or particle size.
Collectively, these findings suggest that, unlike their inflammatory potential in the airways, allergic effects caused by metal nanomaterials may involve various physico-chemical properties, and subsequently, implicate multiple dose metrics.
Roach, Katherine Adair, "Metal Nanomaterials: Immune Effects and Implications of Physicochemical Properties on Sensitization, Elicitation, and Augmentation of Allergic Disease" (2019). Graduate Theses, Dissertations, and Problem Reports. 7385.