Redox modulation and nanotherapies for the treatment of cardiovascular disease

Speaker:

Edward Moreira Bahnson
University of North Carolina

Abstract:

Cardiovascular disease (CVD) is a leading cause of death and disability in the world. Atherosclerosis is a chronic inflammatory disease of large and medium-sized arteries that contributes to major mortality and morbidity of CVD. Severe atherosclerosis, whether present in coronary or peripheral arteries, is commonly treated with percutaneous balloon angioplasty and stenting, endarterectomy, or bypass grafting. Unfortunately, the long-term durability of these procedures is limited due to restenosis, which results in luminal narrowing, and ultimately, vascular occlusion. Therefore, there is a pressing need to develop better ways to treat cardiovascular disease. Reactive oxygen and nitrogen species are indispensable in cellular physiology and signaling. Overproduction of these reactive species or failure to maintain their levels within the physiological range results in cellular redox dysfunction often termed oxidative stress. Redox dysfunction is causally implicated in the severity of vascular dysfunction and CVD. Hence, antioxidant intervention has been pursued as a possible treatment for CVD. However, clinical trials results have been underwhelming. Our lab operates under the hypothesis that delivery of redox therapies should be targeted to the sites of redox dysfunction. Bionanotechnology over the past two decades has generated a number of potential biomedical platforms for drug delivery and diagnostics such as carbon nanotubes, quantum dots, metal nanoparticles, lipid and polymer nanoparticles, dendrimers, nanoscale metal oxides, peptide-based nanostructures, and others. However, the use of these targeted approaches in the CVD field lags behind. Moreover, very few nanomedicine approaches incorporate antioxidants. Implementation of targeted nano-antioxidant therapies has the potential to overcome hurdles associated with systemic delivery of antioxidants, and offers possibilities beyond redox regulation. Moreover, CVD is a very attractive target for nanocarrier-mediated delivery as the vasculature is readily accessible. We currently use cell-mediated approaches as well as customizable nano-carriers to target delivery to sites of vascular inflammation, and thrombosis. Here we present the latest findings of our lab.