Novel alginate-stabilized doxorubicin-loaded nanodroplets for ultrasounic theranosis of breast cancer.
Perfluorocarbon nanoemulsions are a new class of multifunctional stimuli-responsive nanocarriers which combine the properties of passive-targeted drug carriers, ultrasound imaging contrast agents, and ultrasound-responsive drug delivery systems. Doxorubicin-loaded alginate stabilized perflourohexane (PFH) nanodroplets were synthesized via nanoemulsion preparation method and their ultrasound responsivity, imaging, and therapeutic properties were studied. Doxorubicin was loaded into the nanodroplets (39.2nm) with encapsulation efficiency of 92.2%. In vitro release profile of doxorubicin from nanodroplets was an apparently biphasic release process and 12.6% of drug released from nanodroplets after 24h incubation in PBS, pH=7.4. Sonication with 28kHz therapeutic ultrasound for 10min triggered droplet-to-bubble transition in PFH nanodroplets which resulted in the release of 85.95% of doxorubicin from nanodroplets. Microbubbles formed by acoustic vaporization of the nanodroplets underwent inertial cavitation. In the breast cancer mice models, ultrasound-mediated therapy with doxorubicin-loaded PFH nanodroplets showed excellent anti-cancer effects characterized by tumor regression. Complete tumor regression was observed for the group in which doxorubicin-loaded nanodroplets were combined with ultrasound, whereas the tumor growth inhibition of doxorubicin -loaded nanodroplets was 89.6%. These multifunctional nanodroplets, with excellent therapeutic and ultrasound properties, could be promising drug delivery systems for chemotherapeutic application.
Biomaterials Group, Faculty of Biomedical Engineering (Center of Excellence), Amirkabir University of Technology, Tehran, Iran.
Fatemeh
F
Baghbani
Biomaterials Group, Faculty of Biomedical Engineering (Center of Excellence), Amirkabir University of Technology, Tehran, Iran. Electronic address: moztarzadeh@aut.ac.ir.
Fathollah
F
Moztarzadeh
Department of Metallurgy, Faculty of Mining and Metallurgical Engineering, Amirkabir University of Technology, Tehran, Iran.
Jamshid Aghazadeh
JA
Mohandesi
Faculty of New Science and Technologies, University of Tehran, Tehran, Iran.
Fatemeh
F
Yazdian
Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Manijhe
M
Mokhtari-Dizaji
D000464:Alginates / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry / Q000494:pharmacology; D006603:Hexuronic Acids / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D000068936:Theranostic Nanomedicine / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
D000464:Alginates; D004337:Drug Carriers; D006603:Hexuronic Acids; D004317:Doxorubicin; D020723:Glucuronic Acid
Alginate-stabilized nanodroplets; Breast cancer; Ultrasound