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Folic Acid-Functionalized Gadolinium-Loaded Phase Transition Nanodroplets for Dual-Modal Ultrasound/Magnetic Resonance Imaging of Hepatocellular Carcinoma Publisher Pubmed



Maghsoudinia F1 ; Tavakoli MB1 ; Samani RK1 ; Hejazi SH2 ; Sobhani T1 ; Mehradnia F3 ; Mehrgardi MA4
Authors
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Authors Affiliations
  1. 1. Department of Medical Physics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, 81746-73461, Iran
  2. 2. Center for Research in Skin Diseases and Leishmaniasis, Department of Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, 81746-73461, Iran
  3. 3. Biomaterials Group, Faculty of Biomedical Engineering (Center of Excellence), Amirkabir University of Technology, Tehran, Iran
  4. 4. Department of Chemistry, University of Isfahan, Isfahan, 81746-73441, Iran

Source: Talanta Published:2021


Abstract

Dual-modal molecular imaging by combining two imaging techniques can provide complementary information for early cancer diagnosis and therapeutic monitoring. In the present manuscript, folic acid (FA)-functionalized gadolinium-loaded nanodroplets (NDs) are introduced as dual-modal ultrasound (US)/magnetic resonance (MR) imaging contrast agents. These phase-change contrast agents (PCCAs) with alginate (Alg) stabilizing shell and a liquid perfluorohexane (PFH) core were successfully synthesized via the nano-emulsion method and characterized. In this regard, mouse hepatocellular carcinoma (Hepa1-6) as target cancer cells and mouse fibroblast (L929) as control cells were used. The in vitro and in vivo cytotoxicity assessments indicated that Gd/PFH@Alg and Gd/PFH@Alg-FA nanodroplets are highly biocompatible. Gd-loaded NDs do not induce organ toxicity, and no significant hemolytic activity in human red blood cells is observed. Additionally, nanodroplets exhibited strong ultrasound signal intensities as well as T1-weighted MRI signal enhancement with a high relaxivity value of 6.40 mM−1 s−1, which is significantly higher than that of the clinical Gadovist contrast agent (r1 = 4.01 mM−1 s−1). Cellular uptake of Gd-NDs-FA by Hepa1-6 cancer cells was approximately 2.5-fold higher than that of Gd-NDs after 12 h incubation. Furthermore, in vivo results confirmed that the Gd-NDs-FA bound selectively to cancer cells and were accumulated in the tumor region. In conclusion, Gd/PFH@Alg-FA nanodroplets have great potential as US/MR dual-modal imaging nanoprobes for the early diagnosis of cancer. © 2021 Elsevier B.V.
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