Abstract
Previous work has indicated the potential of magnetically functionalized microbubbles to localize and enhance cavitation activity under focused ultrasound exposure in vitro. The aim of this study was to investigate magnetic targeting of microbubbles for promotion of cavitation in vivo. Fluorescently labelled magnetic microbubbles were administered intravenously in a murine xenograft model. Cavitation was induced using a 0.5-MHz focused ultrasound transducer at peak negative focal pressures of 1.2–2.0 MPa and monitored in real-time using B-mode imaging and passive acoustic mapping. Magnetic targeting was found to increase the amplitude of the cavitation signal by approximately 50% compared with untargeted bubbles. Post-exposure magnetic resonance imaging indicated deposition of magnetic nanoparticles in tumours. Magnetic targeting was similarly associated with increased fluorescence intensity in the tumours after the experiments. These results suggest that magnetic targeting could potentially be used to improve delivery of cavitation-mediated therapy and that passive acoustic mapping could be used for real-time monitoring of this process.
Highlights
Ultrasound (US) has previously been found to have therapeutic benefits for a diverse range of applications including physiotherapy (Patrick 1966), cancer treatment (Kremkau 1979), non-invasive surgery and enhancement of the delivery of various agents such as genes (Newman et al 2001), chemotherapeutics (Unger et al 1998) and oncolytic viruses (Carlisle et al 2013)
For fluorescence labelling of the magnetic microbubbles (MMBs), 20 mL of DiI solution was added to the mixture, and the vial was left on a hot plate at 50C for 12 h in a fume hood to allow the chloroform to evaporate
The in vivo distribution and ability to promote cavitation of fluorescently labelled magnetic microbubbles were investigated in a murine tumour model
Summary
Ultrasound (US) has previously been found to have therapeutic benefits for a diverse range of applications including physiotherapy (Patrick 1966), cancer treatment (Kremkau 1979), non-invasive surgery (ter Haar 1999) and enhancement of the delivery of various agents such as genes (Newman et al 2001), chemotherapeutics (Unger et al 1998) and oncolytic viruses (Carlisle et al 2013). The incorporation of iron oxide nanoparticles into the microbubble formulation can enable them to provide contrast enhancement in both ultrasound and magnetic resonance imaging (MRI) (Liu et al 2011; Yang et al 2009). Fluorescent dyes can be used to render microbubbles fluorescent (Lum et al 2006; Patil et al 2011), allowing tracking of the distribution of microbubble components using fluorescence imaging techniques. Both MRI contrast enhancement and fluorescence labelling were employed in the study described here
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