Ultrasound-mediated drug targeting to tumors: Revision of paradigms through intravital imaging

Abstract

In collaboration with Dr. Brian O’Neill (Houston Methodist Research Institute), the intravital fluorescence microscopy was performed using a customized Nikon A1R system to monitor the effect of ultrasound on the extravasation and tissue diffusion of various potential drug carriers including individual polymeric molecules, polymeric micelles, phase-shift nanoemulsions, and nanoemulsion-encapsulated drug. Carrier and drug extravasation and tissue accumulation was compared for the normal and tumor tissue upon intravenous injections to pancreatic tumor bearing mice. This approach allowed for the first time discriminating vascular and tissue compartments in the processes of the ultrasound-mediated drug delivery. Nanoemulsion accumulation in the tumor tissue was much faster than in the normal tissue. Without ultrasound, extravasation coefficient was threefold lower while tissue accumulation rate was two orders of magnitude lower for perfluorocarbon nanodroplets than for polymeric micelles. However, ultrasound a...