Ultrasound and biodegradable nanoparticles for anticancer drug and gene delivery

Abstract

Poor penetration of macromolecular drugs and genes in tumor cells substantially limits efficacy and safety of cancer chemo- and biotherapy. Cavitation induced by interaction of ultrasound with nanoparticles accumulated in tumors due to the enhanced permeability and retention effect may provide efficient drug and gene delivery in tumor cells. Biodegradable polymer (PLGA) air-filled nanoparticles manufactured in our laboratory were used for enhancement of drug and gene delivery in vitro and in vivo in human breast, prostate, or ovarian tumors of nude mice (two tumors in each animal). Our specially designed confocal ultrasound system allowed for irradiation and cavitation detection in vitro and in vivo. It was found that the nanoparticles substantially decrease cavitation threshold and increase cavitation activity in vitro and in vivo. Moreover, we obtained three-fold increase of tumor cell transfection in vivo compared to non-irradiated control tumors of same mice. Substantial tumor necrosis was achieved when macromolecular anticancer drug anti-IGFBP-2 was used in combination with the nanoparticles and ultrasound. Our results indicate that biodegradable polymer nanoparticles and ultrasound can be used for enhancement of drug and gene delivery in tumors. [These studies were supported by the DoD Prostate Cancer Research Program (Grant No. W81XWH-04-1-0247) and Breast Cancer Research Program (Grant No. DAMD17-01-1-0416).]