Neutrophils are part of our innate immune system, the body’s first line of response to disease. When activated normally, neutrophils can fight off pathogens and protect us against disease, however, in some cases, an overactive immune response can lead to inflammatory diseases. The goal of this project is to study the effects of nanoparticle composition, both lipid- and polymer-based, on nanoparticle stability and neutrophil-nanomaterial interactions. I am focusing on modulating the internalization of LNPs and PNPs and activation of the inflammatory cytokines in neutrophils. Inflammatory cytokines play a major role in inflammatory diseases such as pancreatitis, psoriasis, and arthritis. We work with both polymer nanoparticles (PNPs) and LNPs to modulate inflammatory activation for different disease models. We are using the PNPs to target activation pathways as a potential therapy for cancer and the LNPs to inhibit or reduce activation as a therapy for inflammatory diseases. I am looking at how altering their chemical composition affects their stability and their effect on neutrophils. Traditionally, we have used DSPE-PEG(2000)-carboxyllic acid to synthesize our LNPS, but I am using a DSPE-PEG(2000)-maleimide substitution that allows for peptide conjugation. I am testing this by synthesizing the DSPE-PEG(2000)-maleimide LNPs, testing their stability, and performing internalization assays with neutrophils. I am also testing a new formulation of PNPS using a maleimide-based linker. So far in this process, I have found that the DSPE-PEG(2000)-maleimide substitution in the LNPs does not affect its stability. I hypothesize that the DSPE-PEG(2000)-maleimide LNPs conjugated with peptide will be able to increase neutrophil internalization through surface nanomaterial interactions.