Combined cancer therapy by micellar-encapsulated drug and ultrasound.

A new modality of drug targeting to tumors that is under development in our lab is based on the drug encapsulation in polymeric micelles followed by a localized release at the tumor site triggered by focused ultrasound. The rationale behind this approach is that drug encapsulation in micelles decreases systemic concentration of drug and provides for a passive drug targeting to tumors via the enhanced penetration and retention (EPR) effect, thus, reducing unwanted drug interactions with healthy tissues. In addition, polymeric micelles sensitize multidrug resistant (MDR) cells to the action of drugs. Upon the accumulation of drug-loaded micelles at the tumor site, ultrasonic irradiation of the tumor is used to provide for the effective intracellular drug uptake. Ultrasound releases drug from micelles and enhances the intracellular uptake of both released and encapsulated drug. An important advantage of ultrasound is that it is noninvasive, can penetrate deep into the interior of the body, can be focused and carefully controlled. The results of the in vitro application of this technique for delivering anthracyclin drugs to ovarian carcinoma A2780 drug-sensitive and MDR cells are described.