Current status and prospects for microbubbles in ultrasound theranostics

Abstract

Encapsulated microbubbles have been developed over the past two decades to provide both improvements in imaging as well as new therapeutic applications. Microbubble contrast agents are used currently for clinical imaging where increased sensitivity to blood flow is required, such as echocardiography. These compressible spheres oscillate in an acoustic field, producing nonlinear responses which can be uniquely distinguished from surrounding tissue, resulting in substantial enhancements in imaging signal-to-noise ratio. Furthermore, with sufficient acoustic energy the oscillation of microbubbles can mediate localized biological effects in tissue including the enhancement of membrane permeability or increased thermal energy deposition. Structurally, microbubbles are comprised of two principal components – an encapsulating shell and an inner gas core. This configuration enables microbubbles to be loaded with drugs or genes for additional therapeutic effect. Application of sufficient ultrasound energy can release this payload, resulting in site-specific delivery. Extensive pre-clinical studies illustrate that combining microbubbles and ultrasound can result in enhanced drug delivery or gene expression at spatially selective sites. Thus, microbbubles can be used for imaging, for therapy, or for both simultaneously. In this sense, microbubbles combined with acoustics may be one of the most universal theranostic tools.

Pulsed ultrasound enhances the delivery of nitric oxide from bubble liposomes to ex vivo porcine carotid tissue

“…However, these techniques present a trade-off between frequency-dependent ultrasound response and drug-loading capability, which are both highly dependent on particle size. 43 The size discrepancy between the primary peaks could be explained by the use of a NO/C 3 F 8 blend in this study, compared with C 3 F 8 alone used in the report by Endo-Takahashi et al 34 NO is more soluble in lipid than in aqueous solution, 44 yet reacts more readily with oxygen in these environments. NO is further soluble in perfluorocarbon, demonstrated by prolonged release profiles in an in vivo hamster model.…”

Acoustic Cluster Therapy (ACT) enhances the therapeutic efficacy of paclitaxel and Abraxane® for treatment of human prostate adenocarcinoma in mice

“…In recent years, several concepts for ultrasound (US) mediated, targeted drug delivery have been investigated, some with quite encouraging results [7][8][9][10][11][12]. Many of the these approaches explore the use of regular US contrast microbubbles such as Sonovue™ (Bracco Imaging S.p.A, Italy) or Optison™ (GE Healthcare AS, Norway) co-injected with various drug formulations.…”

Ultrasound microbubble-carried PNA targeting to c-myc mRNA inhibits the proliferation of rabbit iliac arterious smooth muscle cells and intimal hyperplasia

“…Application of sufficient ultrasound energy can release this payload, resulting in site-specific delivery. Extensive preclinical studies illustrate that combining microbubbles and ultrasound can result in enhanced drug delivery or gene expression at spatially selective sites (Martin & Dayton, 2013). In the past, the gene or plasmid was connected with microbubbles after they were prepared and was located on the surface of microbubbles (Ji et al, 2012).…”