Polyanhydride Nanoparticle Interactions with Host Serum Proteins and Their Effects on Bone Marrow Derived Macrophage...

An in-depth understanding of the interactions of vaccine delivery vehicles with antigen presenting cells is important for tailoring optimal adjuvant properties. Polymeric nanoparticles have been widely studied as adjuvants and delivery vehicles; however, there is little information regarding the effect of serum protein adsorption onto biomaterials and the effect of this adsorption upon interactions with antigen presenting cells. The current studies analyzed effects of polyanhydride chemistry on serum adsorption to nanoparticles with respect to their uptake by and activation of bone marrow-derived macrophages. Differential effects of serum adsorption based on nanoparticle chemistry were shown to enhance (for 1,6-bis(p-carboxyphenoxy)hexane and sebacic anhydride-based) or reduce (for 1,6-bis(p-carboxyphenoxy)hexane and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane-based) nanoparticle uptake. The observed complex interdependence between nanoparticle chemistry and serum protein adsorption on macrophage activation provided insights that will facilitate the rational design of single-dose nanovaccines developed to induce robust immune responses.