化疗放疗联合控释纳米载体，如声敏感纳米液滴（NDs），可以增强化疗药物的抗癌活性并减少正常组织的副作用。本研究合成了以叶酸功能化的甲氨蝶呤负载的全氟己烷NDs（FA-MTX/PFH@alginate NDs），并对其在乳腺癌超声引导化疗放疗中的潜在应用进行了体外和体内研究。使用NDs和超声处理后，癌细胞（4T1）的存活率和存活分数明显下降，但与X射线照射相结合时下降更为显著。体内外结果证实，MTX负载的NDs具有高度生物相容性，且没有显著溶血作用和器官毒性。此外，体内结果表明，FA-MTX/PFH@alginate NDs在肿瘤区域中有选择性地积累。总之，FA功能化的MTX/PFH@alginate NDs在超声控制药物输送和放疗乳腺癌方面具有良好的治疗和诊断性能。Copyright © 2023 Elsevier Inc. All rights reserved.

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.Copyright © 2023 Elsevier Inc. All rights reserved.