Acoustic vaporization of internalized superheated perfluorocarbon nanodroplets for imaging and macrophage function modulation

Abstract

Ultrasound (US) can detect and interact with its contrast agents, allowing perfluorocarbon-based nanodroplets (NDs) or microbubbles (MBs) to detect and treat tumors in deep tissues. Since NDs given IV passively accumulate in tumor macrophages, we aimed to determine whether phagocytosed perfluorobutane (PFB) NDs that boil at -2 °C, can be vaporized in vivo using a clinical scanner. Should that be possible, PFB NDs can then be used to deliver drugs or genes to modulate macrophage function. We formulated stable PFB NDs and validated their internalization into THP-1 macrophages using confocal microscopy. PFB ND loaded macrophages were then infused into nude rats and US imaging (low MI US imaging, 18H6 transducer) of the liver and spleen performed in vivo using a Siemens Sequoia clinical scanner before and after applying MB destruction pulses (at 1.4 MI, 10L4 transducer). PFB ND-loaded macrophages were not visible using low MI imaging, before applying MB destruction pulses. They immediately vaporized into US visible microbubbles when destruction pulses were applied over the liver and remained visible for many minutes after vaporization. Our current focus is to assess ND-loaded macrophage function before and after ND activation to determine the feasibility of modulating immune function. [Study supported by CPRIT RR150010. RFM is a CPRIT Established Investigator. Siemens ACUSON Sequoia Ultrasound System provided as a loan by Siemens Medical Solutions, USA.]