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Droplet-to-bubble Transition in Phase-shift Nanoemulsions for Tumor Chemotherapy
Natalya Rapoport and Kwon-Ho Nam

Multifunctional nanoemulsion/microbubble nanoparticles that combined properties of drug carriers, ultrasound imaging contrast agents, and enhancers of ultrasoundmediated drug delivery have been developed. At room temperature, the formulations comprised perfluorocarbon nanoemulsions stabilized by biodegradable block copolymers. Under the action of therapeutic ultrasound, nanodroplets converted into microbubbles in the process called acoustic droplet vaporization (ADV). Drug-loaded nanoemulsions released their drug payload under the action of therapeutic ultrasound. The paper reports the results of nanotherapy of ovarian and breast cancerous tumors by paclitaxel-loaded nanoemulsions in combination with tumor-directed 1-MHz therapeutic ultrasound. Tumor accumulation of nanoemulsions was confirmed by ultrasound imaging. Dramatic regression of ovarian and breast cancerous tumors was observed signifying efficient ultrasound-triggered drug release from tumor-accumulated nanodroplets. No therapeutic effect from the nanodroplet/ultrasound combination was observed without the drug, indicating that therapeutic effect was induced by the ultrasound-enhanced chemotherapeutic action of the tumortargeted drug, rather than the mechanical or thermal action of ultrasound itself. The mechanism of the ultrasound-mediated nanochemotherapy is discussed.

Keywords: therapeutic ultrasound, ultrasound-mediated drug delivery, acoustic droplet vaporization, drug targeting, nanochemotherapy, breast cancer, ovarian cancer

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