Ultrasound-guided chemoradiotherapy of breast cancer using smart methotrexate-loaded perfluorohexane nanodroplets

Chemoradiotherapy with controlled-release nanocarriers such as sono-sensitive nanodroplets (NDs) can enhance the anticancer activity of chemotherapy medicines and reduces normal tissue side effects. In this study, folic acid-functionalized methotrexate-loaded perfluorohexane NDs with alginate shell (FA-MTX/PFH@alginate NDs) were synthesized, characterized, and their potential for ultrasound-guided chemoradiotherapy of breast cancer was investigated in vitro and in vivo. The cancer cell (4T1) viabilities and surviving fractions after NDs and ultrasound treatments were significantly decreased. However, this reduction was much more significant for ultrasound in combination with X-ray irradiation. The in vitro and in vivo results confirmed that MTX-loaded NDs are highly biocompatible and they have no significant hemolytic activity and organ toxicity. Furthermore, the in vivo results indicated that the FA-MTX/PFH@alginate NDs were accumulated selectively in the tumor region. In conclusion, FA-functionalized MTX/PFH@alginate NDs have a great theranostic performance for ultrasound-controlled drug delivery in combination with radiotherapy of breast cancer. In the present study, folic acid-functionalized methotrexate-loaded perfluorohexane NDs with alginate shell (FA-MTX/PFH@alginate NDs) were successfully synthesized. These nanostructures were applied for the smart ultrasound-guided chemoradiotherapy of breast cancer. The in vitro studies on NDs including bio- and hemo- compatibility, and cytotoxicity assessments after US and X-ray exposures were performed. Then, the in vivo studies demonstrated that FA-MTX/PFH@alginate NDs with low organ toxicity and suitable biodistribution offered high inhibitory effects on tumor growth in combination with US exposure and X-ray irradiation. [Display omitted]