Student: Jared Johns
Project Mentors: Dr. Mark K.C. Wang – SBHSE
Dr. Scott Beeman – SBHSE
Dr. Sarah Stabenfeldt - SBHSE
YouTube Link: View the video link below before joining the zoom meeting
Zoom Link: https://asu.zoom.us/j/2740708059
Zoom meeting time: 9am - 11am
Abstract
Atherosclerosis, the leading cause of death in the United States, begins with maladaptive inflammation in the arterial wall causing mass recruitment of leukocytes to the activated vascular endothelium. The chronic inflammation, in the presence of cardiovascular risk factors, contributes to the development of atherosclerotic plaque. Anti-inflammatory therapies have been used with some success in reducing the onset of atherosclerosis. However, the lack of specificity of these therapies often increases risk for other medical problems and limits the effectiveness of the treatment. Improved specificity can be achieved through biomimetic nanoparticles, which have shown great promise in the targeted delivery of drugs and synthetic nucleic acids into diseased tissues, including injured vasculature. By adopting the cell membrane-cloaking approach, we aim to develop a novel class of hybrid nanoparticles with poly(lactic-co-glycolic) acid (PLGA) cores to be enclosed in the plasma membrane of mouse leukocytes. We hypothesize that the leukocyte membrane cloaking facilitates the binding of the nanoparticle to activated endothelium and that the resulting nanoparticles can serve as nanocarriers to deliver anti- inflammatory agents specifically to the vessel wall in inflammatory state. The objective of my applied project is to establish a protocol for the preparation and characterization of the leukocyte membrane- coated nanoparticles (LNPs). Specifically, double emulsion under various concentrations of the emulsifier (i.e., polyvinyl alcohol, or PVA) and sonication intensity have been performed to determine the optimal conditions for the preparation of polymeric cores. Using dynamic light scattering (DLS), I found that nanoparticle size decreased as PVA concentration increased, with particle size minimized using 1% PVA. Moreover, higher amplitude sonication resulted in decreased polydispersity index and particle size across all PVA concentrations, with more pronounced changes under low PVA conditions. The next steps are to enclose the PLGA cores with the leukocyte membrane isolated from mouse blood, characterize the physiochemical properties with DLS and transmission electron microscopy, and measure the LNP uptake efficiency in cultured vascular endothelial cells. Development of these membrane-coated nanoparticles will hopefully provide a tissue-specific delivery vector, thereby improving atherosclerosis therapy.