(590f) Endothelial Targeting of Antioxidant Polymer Nanoparticles for the Suppression of Vascular Oxidative Stress

Vascular oxidative stress is a key pathological process in a variety of disease states (e.g., ischemia ? reperfusion injury, hypoxia, and acute lung or renal injury). Oxidative stress is characterized by the formation of a wide range of reactive oxygen species (e.g., super oxide, hydrogen peroxide, and peroxy lipids), which can cause severe DNA, protein, and lipid damage leading to cellular dysfunction and death. This type of injury results in a degenerative cycle of propogative damage. It is possible to suppress this injury through the addition of free radical scavengers (e.g., dietary antioxidants), which can intercept oxidation of cellular components and thereby attenuate this damage. However, in order for this therapy to be effective, enough antioxidants must be delivered to the site of injury for sufficient duration to be effective. We have previously demonstrated the use of an antioxidant polymer, poly(trolox), to suppress general vascular oxidative stress. In this work, we evaluate the ability of platelet endothelial cell adhesion molecule (PECAM) targeted poly(trolox) nanoparticles ability to suppress injury in a human umbilical vein endothelial cell (HUVEC) model. By incorporating targeting antibodies on the surface of these nanoparticles we see significant attachment of polymeric carriers to endothelial cells as compared to untargeted polymer nanoparticles. We studied the effects of carrier degradation in suppression of oxidative stress, along with durational studies to determine length of protection provided in a HUVEC cell culture model. The results demonstrate the capability of developing a targeted antioxidant drug delivery system in order to suppress the damaging effects of radical formation contributing to vascular oxidative stress.