Controlled Drug Delivery to Drug-Sensitive and Multidrug Resistant Cells: Effects of Pluronic Micelles and Ultraso and Ultrasound

摘要

We are developing a new modality of drug targeting to tumors, based on drug encapsulation in polymeric micelles followed by localized release at the tumor site triggered by focused ultrasound. In the present paper, effects of micelles and ultrasound on the intracellular uptake and cytotoxicity of anthracycline drugs in drug-sensitive and multidrug resistant (MDR) cells are discussed. Significant sensitization of MDR cells by Pluronic micelles and ultrasound was observed, presumably resulting from the suppression of the intracellular energy metabolism and the permeabilization of the cytoplasmic acidic vesicles, which enhanced drug uptake and allowed drug trafficking into cell nuclei. Both effects were enhanced by ultrasound.