Convertible perfluorocarbon droplets for cancer detection and therapy

To enhance the detection and treatment of solid tumours, submicron droplets of liquid perfluorocarbon (PFC) have been developed which can accumulate in tumours by extravasation, and which can subsequently convert to highly echogenic gas bubbles using bursts of high-pressure ultrasound. One aim of droplet formulation is to balance the requirements of physical stability with acoustic convertibility. In this study, droplets ranging in size from 200nm to 2μm, composed of liquid perfluoropentane (PFP) or pefluorohexane (PFH) encapsulated by a fluorosurfactant were synthesized by extrusion and sonication. Droplet stability was assessed using fluorescence microscopy of incorporated quantum dots following incubation with macrophage cells over 4 hours. The impact on stability of depositing 1-3 layers of polyelectrolytes on the droplet surface was also assessed. The rate of coalescence was significantly reduced for droplets coated with 3 polyelectrolyte layers. At 10 MHz, the conversion threshold MI decreased from greater than 4 for 200nm PFP to less than 2 for 2μm PFP droplets, and did not depend strongly on the addition of polyelectrolytes. Resulting bubbles from vaporization persisted for at least Is and were detectable using clinical nonlinear contrast detection pulse sequences, however, the conversion of droplets within cells resulted in cell death.