期刊
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
卷 61, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.jddst.2020.102288
关键词
Gadolinium-carbon dots; Bevacizumab; Dual-modal imaging; Magnetic resonance imaging; Fluorescence imaging; Hepatocellular carcinoma
资金
- Vice Presidency of Research and Technology of Isfahan University of Medical Sciences, Isfahan, Iran [198171]
- University of Isfahan Research Council
Dual-targeted gadolinium-carbon dots functionalized with Bevacizumab and/or folic acid showed high relaxivities and strong fluorescence, with low toxicity. Functionalization significantly improved the uptake by cancer cells and enhanced diagnostic accuracy.
In this study, single- and dual-targeted gadolinium-carbon dots (Gd-CDs) with Bevacizumab (BEV) and/or folic acid (FA) were developed as dual-modal fluorescence and magnetic resonance (FL/MR) imaging nanoprobes. GdCDs were prepared by a single-pot hydrothermal route using citric acid, ethylenediamine, and Gd-DO3A-butrol (Gadovist) as the starting materials. Mouse hepatocellular carcinoma (Hepal-6) cell line was selected as cancer cells, while mouse fibroblast (L929) was used as a normal cell line. Gd-CDs, Gd-CDs-FA, Gd-CDs-BEV, and GdCDs-FA-BEV exhibited the high relaxivities (r(1)) of 7.98, 7.83, 7.61, and 6.03 mk4(-1) s(-1), respectively, being considerably more than the clinical Gd-DO3A-butrol contrast agent (r(1) = 4.01 mM(-1 )s(-1)). Moreover, they exhibited strong fluorescence with a fluorescence quantum yield (QY) of 49.94%, 61.22%, 82.5%, and 83.67%, respectively. MTT assays on cancer and normal cells showed that various synthesized Gd-CDs on both cell lines have low toxicity. Inductively coupled plasma optical emission spectrometry (ICP-OES) analysis revealed that Gd-CDs-FA-BEV uptake by Hepal-6 cells was 5-fold as much as the non-targeted Gd-CDs after 24 h incubation. Functionalization of Gd-CDs with Bevacizumab and/or folic acid improves the diagnostic sensitivities and specificities, making them ideal contrast agents for MRI as well as ideal fluorophores for fluorescence imaging.
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