Novel Strategies for Ultrasound Diagnostics and Therapeutics by Micro/Nanobubbles

Theranostics is a novel concept that combines diagnostics and therapeutics. In the field of diagnostics, various pieces of medical equipment are commonly used, such as X-ray computed tomography,magnetic resonance imaging,positron emission tomography,and sonography. Because of physical energy within these different pieces of equipment,ultrasound is a useful tool for theranostics,and it is particularly suitable for diagnostics with sonography and therapeutics with hyperthermia for cancer. Recently,microbubbles were recognized as an effective type of agent for imaging blood flow in tumors. In particular,Sonazoid,which is a commercially available microbubble,has been used for detection of hepatic tumors. In addition,microbubbles are useful tools for theranostics because they can be used not only as an ultrasound contrast imaging agent but also as an enhancer for hyperthermia with therapeutic ultrasound. To improve the accessibility of microbubbles in the deep tissue,researchers are developing various types of smaller bubbles such as the submicron-sized nanobubble. We have also developed novel liposomal bubbles(Bubble liposomes),which consist of entrapped perfluoropropane gas in a lipid bilayer. Bubble liposomes have several advantages over existing technologies,such as they can be used as ultrasound imaging agents,it is easy to modify the targeting molecules on their surfaces,and they are highly applicable for the enhancement of hyperthermia with therapeutic ultrasound. In summary,the combination of ultrasound and micro/nanobubbles would allow for the development of an ideal method for noninvasive theranostics. In this review, we will introduce recent developments on ultrasound theranostics using microbubbles and nanobubbles such as Bubble liposomes.