PROJECT SUMMARY/ABSTRACT Traditional means to identify and treat arterial disease are hampered by their inability to direct therapeutics to local atheroma components. Novel targeted acoustic delivery agents (liposomes) with novel ultrasound delivery methodologies may overcome these problems. Liposomes are phospholipid vesicles enclosing an aqueous space. We have developed a unique methodology that, by process and composition, makes these liposomes echogenic. This formulation allows modification for antibody conjugation and therapeutic (drug/bioactive gas) incorporation. Work by our group has demonstrated that these formulations can incorporate and deliver therapeutics to cells, while retaining their echogenic properties. The latter is important as the addition of therapeutic ultrasound has a unique effect on these echogenic liposomes by increasing cellular delivery. Our principal aim is to develop a model carrier and a technique that has the ability to incorporate a therapeutic with delivery to a target structure while retaining the therapeutic?s effects. We have: a) developed robust therapeutic echogenic immunoliposomes (ELIP); b) developed ultrasound parameters for therapeutic delivery of loaded ELIP and c) determined the efficacy of our therapeutic ELIP in slowing/stabilizing atheroma progression. We will now translate our discoveries for use in unstable atheroma and translate them into the clinical setting. We will develop a novel ultrasound methodology for therapeutic delivery into the coronary arterial beds. We will evaluate our therapeutic-loaded carriers with ultrasound activation in vivo and translate our optimal strategy into the clinical setting. Development of these agents and techniques would have far reaching implications for the treatment of chronic high risk atherosclerosis.