Sialic Acid Binding Nanoparticle to Inhibit Inflammation

Abstract

Inflammation is an excellent biological response that our bodies have developed to fight off foreign objects that have made their way into our bodies. In some cases, the inflammation becomes chronic as the immune system attacks healthy tissue or is unable to heal an injury. In this project the overall goal is to inhibit the inflammatory cascade using synthetic nanoparticles that mimic lectins - the natural glyco-bindning proteins. The particles bind sialic acid, a monosaccharide that is highly up-regulated during inflammation, and inhibits protein-protein or cell-cell interactions depending on size. The targeting moeity of the nanoparticles are phenylboronic acid (PBA) attached to branched polyethylenimine (PEI) polymers, named PBA-PEI. Isother-mal titration calorimetry (ITC) and UV data show that the PBA-PEI have very high specificity and affinity towards sialic acid compared to other monosaccharides and previously published materials. Cytotoxic evaluation show that the synthesized nanoparticles are non-toxic. Furthermore, we demonstrate biological relevance of our approach in preliminary studies, where the larger nanoparticles inhibited proinflammatory activation.