Iron-dexamethasone nanoparticles mitigate acute neutrophilic inflammation

Neutrophils are the primary immune cell type present within the blood and the first to arrive at sites of inflammation. As such, neutrophils set the stage for how the inflammatory response progresses and resolves. In some cases of non-resolving inflammation, excessive neutrophil accumulation can cause tissue damage. Accordingly, maintaining tight control over their recruitment and behavior at sites of inflammation is paramount. Historically, corticosteroids have been used to modulate inflammation, but they are associated with systemic side effects that have limited their use. Here, we developed an iron-dexamethasone nanoparticle (DexOx NP) therapeutic that modulates neutrophil behavior and reroutes neutrophils away from sites of inflammation. DexOx NPs inhibit neutrophil activation, as indicated by prevention of L-selectin shedding and reduced neutrophil extracellular trap formation. Furthermore, treatment with DexOx NPs in a murine acute lung injury model significantly reduced the total number of neutrophils in the bronchoalveolar lavage fluid while avoiding the side effects of systemic soluble dexamethasone phosphate delivery. Thus, DexOx NPs represent a new option to control non-resolving neutrophilic inflammation.