THE REDUCTION OF NEUTROPHIL POPULATIONS IN INFLAMMATORY CONDITIONS USING CD177-MEDIATED PH-SENSITIVE FUSOGENIC NANOPARTICLES

Abstract

Neutrophils serve a vital role in innate immune defense against bacterial and fungal pathogens. While neutrophils function in the most robust immune defense, they can also play a detrimental role in inflammatory conditions that can even lead to death. Reduction of complement factor 5a receptor-1 (C5aR1) suppresses neutrophils to get signals to migrate to the affected site, thus reducing inflammation. Previous research conducted by Miettinen et al. in 2018 demonstrated that 67-82% of mouse neutrophil C5aR1 protein was knocked down by siRNA and antisense oligonucleotides (ASO) using CD177-mediated hybrid polymerized liposome nanoparticles (HPLN). Approximately 30% of HPLNs were degraded in the endosome. In this proposal, I will incorporate a pH sensitive Glutamic acid-Alanine-Leucine-Alanine (GALA) peptide on the surface of HPLN, which will help the HPLN escape the endosome. I hypothesize this will completely and transiently knock down neutrophil C5aR1.