Ultrasound-triggered drug targeting of tumors in vitro and in vivo

The new modality of drug targeting of tumors that we are currently developing is based on drug encapsulation in polymeric micelles, followed by the 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, diminishes intracellular drug uptake by normal cells, and provides passive drug targeting of tumors, thus reducing unwanted drug interactions with healthy tissues. Ultrasound irradiation is used to release drug from micelles at the tumor site and to enhance the intracellular drug uptake by tumor cells. 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. Here we describe factors involved in the ultrasound interaction with viable cells in the absence and presence of drug carriers and anti-cancer drugs. We present in vivo effects of 1 MHz ultrasound on drug biodistribution, intratumoral distribution, and survival rates of immuno-compromised athymic nu/nu mice bearing ovarian carcinoma tumors.