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

Roghayeh Kamran Samani; Fatemeh Maghsoudinia; Fatemeh Mehradnia; Seyed Hossein Hejazi; Mohsen Saeb; Tayebe Sobhani; Zohreh Farahbakhsh; Masoud A Mehrgardi; Mohamad Bagher Tavakoli

doi:10.1016/j.nano.2022.102643

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

Nanomedicine. 2023 Feb:48:102643. doi: 10.1016/j.nano.2022.102643. Epub 2022 Dec 28.

Authors

Roghayeh Kamran Samani¹, Fatemeh Maghsoudinia², Fatemeh Mehradnia³, Seyed Hossein Hejazi⁴, Mohsen Saeb⁵, Tayebe Sobhani⁵, Zohreh Farahbakhsh⁶, Masoud A Mehrgardi⁷, Mohamad Bagher Tavakoli⁸

Affiliations

¹ Department of Medical Physics and Radiology, School of Allied Medical Sciences, Shahrekord University of Medical Sciences, Shahrekord, Iran; Department of Medical Physics, School of Medicine, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran.
² Department of Medical Imaging and Radiation Sciences, Faculty of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
³ Division of Molecular Therapeutics and Formulation, School of Pharmacy, University of Nottingham, NG7 2RD, UK.
⁴ Skin Diseases and Leishmaniasis Research Center, Department of Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran.
⁵ Department of Medical Physics, School of Medicine, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran.
⁶ Department of Medical Parasitology and Mycology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
⁷ Department of Chemistry, University of Isfahan, Isfahan 81746-73441, Iran. Electronic address: m.mehrgardi@chem.ui.ac.ir.
⁸ Department of Medical Physics, School of Medicine, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran. Electronic address: mbtavakoli@mui.ac.ir.

PMID: 36584739
DOI: 10.1016/j.nano.2022.102643

Abstract

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.

Keywords: Chemoradiotherapy; Methotrexate; Perfluorohexane nanodroplets; Smart drug delivery system; Ultrasound.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alginates
Breast Neoplasms* / drug therapy
Cell Line, Tumor
Chemoradiotherapy
Female
Humans
Methotrexate / pharmacology
Nanoparticles*
Ultrasonography, Interventional

Substances

Methotrexate
perflexane
Alginates