Targeting vascular inflammation

Targeting vascular inflammation

Inflammation is involved in nearly all vascular pathologies, including ischemia-reperfusion injury, stroke, atherosclerosis, restenosis, autoimmunity, injury, and infection. It is characterized by a cascade of events that culminates in changes in the expression pattern of molecules on the surface of vascular endothelial cells. These molecular determinants are cell adhesion molecules that promote recruitment of leukocytes, which then mediate immune responses, tissue repair, and, in some cases, exacerbate disease. Thus, endothelial cell adhesion molecules are markers of inflammation that can be exploited for detection or treatment of vascular diseases. Examples include P- and E-selectin, which mediate the initial stage of recruitment by slowing cells via a dynamic interaction called rolling. Vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) support firm arrest of activated leukocytes. Optimally targeting these adhesion molecules with nanomaterial carriers will require knowledge of the expression levels and dynamics. We are taking these factors into account, while also utilizing protein engineering, nanoparticle synthesis, and biophysical modeling approaches to better understand and engineer nanoparticle carrier adhesion dynamics.