Ultrasound-mediated nanoparticle drug delivery in an in vivo tumor model

Abstract

One of the exciting possible future clinical uses of ultrasound is site-targeted drug delivery using focused acoustic energy. In an earlier study, it was shown that ultrasound exposure promoted lipid delivery from nanoparticles into melanoma cells in culture [Crowder et al., UMB 2005]. In order to extend the study to in vivo situations, a novel, combined ultrasound therapeutic and imaging system was developed. The system consisted of a therapeutic transducer (−6-dB BW 1.1 to 2.3 MHz; natural focus 8 cm; f-number 1) with a centrally located and coregistered imaging transducer connected to a commercial ultrasound imaging system. The system provided capability for arbitrary acoustic excitation, electronic axial steering, and mechanical translation of the therapy transducer as well as real-time acquisition of images. The device was tested on bilateral murine tumor models (MDA435). Tumor images provided real-time feedback for treatment planning. The animals were injected with perfluorooctyl bromide nanoparticles targeted to αvβ3 integrin and with a radioactive complex. Initial results showed that application of therapeutic ultrasound affected the delivery of the radioactive complex as measured by radioactivity 24 h postinjection. Experimental results and experiences will be presented detailing the importance of imaging for in vivo treatment guidance and planning.