Droplet-To-Bubble Transition in Phase-Shift Nanoemulsions for Tumor Chemotherapy

摘要

Multifunctional nanoemulsion/microbubble nanoparticles that combined properties of drug carriers, ultrasound imaging contrast agents, and enhancers of ultrasound-mediated drug delivery have been developed. At room temperature, the formulations comprised periluorocarbon nanoemulsions stabilized by biodegradable block copo-lymers. 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/ultra-sound combination was observed without the drug, indicating that therapeutic effect was induced by the ultrasound-enhanced chemotherapeutic action of the tumor-targeted drug, rather than the mechanical or thermal action of ultrasound itself. The mechanism of the ultrasound-mediated nanochemotherapy is discussed.