(679b) Effects On Macrophage Activation Profiles Induced by Adsorption of Serum Proteins Onto Polyanhydride Nanoparticles

Biodegradable polymers have shown promising characteristics as adjuvants and/or delivery vehicles by enhancing antigen presentation compared with soluble protein. The chemical and physical properties of these materials can be tailored to enhance their interactions with antigen presenting cells (APCs). In particular, polyanhydride nanoparticles exhibit desirable characteristics as adjuvants such as immunomodulation, sustained antigen release, and stabilization of protein antigens. Upon in vivo administration, serum proteins coat the surface of nanoparticles, potentially affecting their interactions with immune cells. For example, opsonization of the particles may be affected and this enhances cell phagocytosis by the stimulation of different receptors (e.g., Fcγ, mannose) and by the activation of the complement cascade. Analysis of these interactions is necessary to rationally select and shape the desired immune response. It is known that complement receptor 3 (CR3) is required to induce phagocytosis through its interaction with iC3b and modulation of IL-12 production by APCs.

In this work, the effect of serum protein adsorption onto polyanhydride nanoparticles following stimulation of CR3-deficient (CR3^-/-) mice macrophages on the internalization and activation of these cells was investigated. Polyanhydride nanoparticles based on sebacic acid (SA), 1,6-bis-(p-carboxyphenoxy)hexane (CPH), and 1,8-bis-(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) were used in this study. The profile of adsorbed serum proteins on the surface of the nanoparticles was a function of polymer chemistry. This resulted in different activation phenotypes of the macrophages. The results also showed that the CR3-mediated pathway was important for the uptake of polyanhydride nanoparticles by macrophages. These studies have important implications for the in vivo performance of nanoparticle-based systems for vaccine delivery.