Ultrasonic nanotherapy of breast cancer using novel ultrasound-responsive alginate-shelled perfluorohexane nanodroplets: In vitro and in vivo evaluation.

Development of a new class of multifunctional ultrasound-responsive smart nanocarriers that combine therapeutic properties with diagnostic imaging has gained great attention in recent years. Here, we describe the results of ultrasonic nanotherapy of breast cancer using novel alginate-stabilized perfluorohexane nanodroplets. Doxorubicin (Dox)-loaded multifunctional nanodroplets (Dox-NDs) were synthesized via nanoemulsion process and evaluated in vitro and in vivo with focus on cytotoxicity, hemolytic activity, biodistribution, biosafety, and antitumor activity. Echogenic property of nanodroplets was confirmed by B-mode ultrasound imaging. Tumor therapy using Dox-NDs combined with sonication (Dox-ND-US) resulted in strong in vivo antitumor activity characterized by tumor regression which could be because of on demand efficient ultrasound-aided drug release from nanodroplets in tumor tissue under the action of ultrasound. Dox concentration in tumor area for Dox-ND-US treated group reached 10.9μg/g after sonication for 4min (28kHz, 0.034W/cm2), which was 5.2-fold higher compared to non-sonicated Dox-NDs group. The cardiotoxicity of Dox-NDs was much lower than that of free Dox and no hemolytic activity was observed for Dox-NDs. Strong therapeutic effect of these multifunctional nanodroplets combined with their ultrasound-contrast property indicated that this drug delivery system has a great potential in smart cancer-therapy.