ICAM-1 Targeted Delivery and Biodistribution of Protein Nanoparticles

Inflammation is a regulated response to injury or infection that protects and repairs the body. When an inflammatory response is unregulated, hyper-inflammation can lead to organ damage and endothelium dysfunction. Recently, SARS-CoV-2 infections have been the cause of severe pneumonia, cardiovascular complications, and organ failures. Severe infections are accompanied by pulmonary hyper-inflammation and induced vascular endothelium damage. Protein nanoparticles can be modified to target and deliver anti-inflammatory cargo to the source of inflammation which is primarily among vascular endothelium cells. Specifically, this thesis explores the fabrication and optimization of protein nanoparticles with conjugated antibodies to specifically target endothelial cells. Protein nanoparticle targeting and uptake were confirmed in the cytoplasm of cultured Human Umbilical Vascular Endothelial Cells (HUVEC) using confocal microscopy and flow cytometry. Lastly, the biodistribution of these nanoparticles was assessed in healthy mice to understand the targeting of protein nanoparticles conjugated with targeting antibodies in vivo. Overall, this thesis demonstrates the impact that conjugated antibodies have on enhancing intracellular delivery and the biodistribution of these nanoparticles in vivo.M.S