Targeted Delivery of Antioxidant Nanoparticles to Inhibit Restenosis

Cardiovascular disease is the leading cause of death globally, often resulting from the development of atherosclerosis. Common surgical interventions, such as balloon angioplasty, repeatedly fail due to the re-narrowing of an artery over time, a process called restenosis. Neointimal hyperplasia, the proliferation and migration of cells that leads to restenosis, is driven by reactive oxygen species (ROS). In natural response to injury, macrophages target inflammation in the vasculature. This response provides a strategy for targeted delivery of therapeutics, but it is unknown whether macrophages can deliver antioxidant enzymes to sites of arterial injury. We hypothesize that macrophages can be loaded with antioxidant enzyme nanoparticles (NPs) to deliver enzymatically active catalase (CAT) or superoxide dismutase (SOD) in order to decrease ROS and hence, inhibit neointimal hyperplasia. Using dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA), catalase NPs and SOD NPs size and dispersity were characterized. Encapsulated enzymes were enzymatically active and stable for 7 days, indicating that nanoparticles do not inhibit enzymatic activity. Macrophage uptake of enzyme-loaded NPs was assessed using fluorescence microscopy. Uptake by murine macrophages (RAW 264.7) peaked at 2 hours with macrophages engulfing more fluorescently-labeled enzyme-loaded NPs than free enzyme. Using macrophages with antioxidant enzyme-loaded nanoparticles is a viable approach to deliver active catalase or SOD, resulting in a targeted delivery system for sites of restenosis. This strategy would present a great advantage to the medical world, as preparation of targeted drug therapy could be executed ex vivo with the potential to be implemented back into the patient.Bachelor of Scienc