Recent advances in ultrasound-based diagnosis and therapy with micro- and nanometer-sized formulations

Ultrasound (US) is one of the most frequently used imaging methods in the clinic. The broad spectrum of its applications can be increased by the use of gas-filled microbubbles (MB) as ultrasound contrast agents (UCA). In recent years, also nanoscale UCA like nanobubbles (NB), echogenic liposomes (ELIP) and nanodroplets have been developed, which in contrast to MB, are able to extravasate from the vessels into the tissue. New disease-specific UCA have been designed for the assessment of tissue biomarkers and advanced US to a molecular imaging modality. For this purpose, specific binding moieties were coupled to the UCA surface. The vascular endothelial growth factor receptor-2 (VEGFR-2) and P-/E-selectin are prominent examples of molecular US targets to visualize tumor blood vessels and inflammatory diseases, respectively. Besides their application in contrast-enhanced imaging, MB can also be employed for drug delivery to tumors and across the blood-brain barrier (BBB). This review summarizes the development of micro- and nanoscaled UCA and highlights recent advances in diagnostic and therapeutic applications, which are ready for translation into the clinic.