The long-term objective of this Program of Excellence in Nanotechnology (PEN) is to design nanodevices for the analysis, diagnosis, monitoring, and treatment of vulnerable atherosclerotic plaques. It is generally believed that the rupture of atherosclerotic plaques accounts for ~70% of myocardial infarcts. Plaques differ in their structure and composition. Those with a thin fibrous cap, increased lipid content, and adherent inflammatory cells are referred to as “vulnerable” and are highly susceptible to rupture. This PEN is a partnership between The Burnham Institute (La Jolla, Ca), The Scripps Research Institute (La Jolla, Ca), and the California NanoSystems Institute (CNSI) at the University of California at Santa Barbara. We will use the underlying biochemistry that drives the pathophysiology of atheroma as a wedge to target and control nanodevices directed to vulnerable plaque. This PEN will work at the interface of biochemical design and nanoscience. We will create five fundamental and modular building blocks; Targeting Elements, Delivery Vehicles, Selfassembling Polymers, Molecular Switches, and Bio-Nanoelectromechanical systems (Bio- NEMS). These building blocks will serve as a platform for the creation of novel nanodevices for treating atheroma.