Tunable microbubbles for antivascular ultrasound

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Abstract Antivascular ultrasound is a novel approach that uses low-amplitude ultrasound and microbubbles to treat cancers. In the presence of ultrasound irradiation, microbubbles act as microscopic sources that convert acoustic energy into heat through viscous damping of oscillating bubbles. The localized intravascular heating damages endothelial cells and disrupt tumor vasculature. Thus microbubbles function as both energy source and ultrasound wave beacons to deliver acoustic energy locally to the vascular endothelium. The goals of the research are to model ultrasound-enhanced heating mathematically and to use the model to guide the synthesis of microbubbles using novel microfluidics techniques. The proposal has three Specific Aims. Specific Aim 1 is to use computational modeling to identify mechanical properties and bubble size distribution that produce maximum thermal effects. Specific Aim 2 will be to synthesize microbubbles of desired size distribution and shell properties. Specific Aim 3 will test the efficacy of microbubble preparations in flow phantoms and preclinical animal model. The experimental results will be compared with theoretical calculations. Thus both mathematical modeling and the unique method of synthesis will provide an integrated approach for antivascular therapy. The proposed research develops a completely new ultrasound cancer treatment with significant advantages over existing techniques. We anticipate that the knowledge gained from the proposed research will lead to a new form of antivascular therapy for treating cancers.