Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin–avidin-specific binding

Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin–avidin-specific binding

Yongjun Liu,1 Xiaoyun Wu,1 Xiaohe Sun,1 Dan Wang,1 Ying Zhong,1 Dandan Jiang,1 Tianqi Wang,1 Dexin Yu,2 Na Zhang1 1School of Pharmaceutical Science, Shandong University, 2Department of Radiology Medicine, Qilu Hospital, Jinan, People’s Republic of China Abstract: Developing magnetic reso...

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Autores principales: Liu YJ, Wu XY, Sun XH, Wang D, Zhong Y, Jiang DD, Wang TQ, Yu DX, Zhang N
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2017
Materias:
MRI
contrast agent
VEGFR
biotin-avidin reaction
relaxivity
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/5cdb75c328334483a40cc6a4e1086fea
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spelling oai:doaj.org-article:5cdb75c328334483a40cc6a4e1086fea2021-12-02T00:27:13ZDesign, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin–avidin-specific binding1178-2013https://doaj.org/article/5cdb75c328334483a40cc6a4e1086fea2017-07-01T00:00:00Zhttps://www.dovepress.com/design-synthesis-and-evaluation-of-vegfr-targeted-macromolecular-mri-c-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yongjun Liu,1 Xiaoyun Wu,1 Xiaohe Sun,1 Dan Wang,1 Ying Zhong,1 Dandan Jiang,1 Tianqi Wang,1 Dexin Yu,2 Na Zhang1 1School of Pharmaceutical Science, Shandong University, 2Department of Radiology Medicine, Qilu Hospital, Jinan, People’s Republic of China Abstract: Developing magnetic resonance imaging (MRI) contrast agents with high relaxivity and specificity was essential to increase MRI diagnostic sensitivity and accuracy. In this study, the MRI contrast agent, vascular endothelial growth factor receptor (VEGFR)-targeted poly (l-lysine) (PLL)-diethylene triamine pentacetate acid (DTPA)-gadolinium (Gd) (VEGFR-targeted PLL-DTPA-Gd, VPDG), was designed and prepared to enhance the MRI diagnosis capacity of tumor. Biotin-PLL-DTPA-Gd was synthesized first, then, VEGFR antibody was linked to biotin-PLL-DTPA-Gd using biotin–avidin reaction. In vitro cytotoxicity study results showed that VPDG had low toxicity to MCF-7 cells and HepG2 cells at experimental concentrations. In cell uptake experiments, VPDG could significantly increase the internalization rates (61.75%±5.22%) in VEGFR-positive HepG2 cells compared to PLL-DTPA-Gd (PDG) (25.16%±4.71%, P<0.05). In MRI studies in vitro, significantly higher T1 relaxivity (14.184 mM-1 s-1) was observed compared to Magnevist® (4.9 mM-1 s-1; P<0.01). Furthermore, in vivo MRI study results showed that VPDG could significantly enhance the tumor signal intensity and prolong the diagnostic time (from <1 h to 2.5 h). These results indicated that macromolecular VPDG was a promising MRI contrast agent and held great potential for molecular diagnosis of tumor. Keywords: MRI, contrast agent, VEGFR, biotin–avidin reaction, relaxivityLiu YJWu XYSun XHWang DZhong YJiang DDWang TQYu DXZhang NDove Medical PressarticleMRIcontrast agentVEGFRbiotin-avidin reactionrelaxivityMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 5039-5052 (2017)
institution DOAJ
collection DOAJ
language EN
topic MRI
contrast agent
VEGFR
biotin-avidin reaction
relaxivity
Medicine (General)
R5-920
spellingShingle MRI
contrast agent
VEGFR
biotin-avidin reaction
relaxivity
Medicine (General)
R5-920
Liu YJ
Wu XY
Sun XH
Wang D
Zhong Y
Jiang DD
Wang TQ
Yu DX
Zhang N
Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin–avidin-specific binding
description Yongjun Liu,1 Xiaoyun Wu,1 Xiaohe Sun,1 Dan Wang,1 Ying Zhong,1 Dandan Jiang,1 Tianqi Wang,1 Dexin Yu,2 Na Zhang1 1School of Pharmaceutical Science, Shandong University, 2Department of Radiology Medicine, Qilu Hospital, Jinan, People’s Republic of China Abstract: Developing magnetic resonance imaging (MRI) contrast agents with high relaxivity and specificity was essential to increase MRI diagnostic sensitivity and accuracy. In this study, the MRI contrast agent, vascular endothelial growth factor receptor (VEGFR)-targeted poly (l-lysine) (PLL)-diethylene triamine pentacetate acid (DTPA)-gadolinium (Gd) (VEGFR-targeted PLL-DTPA-Gd, VPDG), was designed and prepared to enhance the MRI diagnosis capacity of tumor. Biotin-PLL-DTPA-Gd was synthesized first, then, VEGFR antibody was linked to biotin-PLL-DTPA-Gd using biotin–avidin reaction. In vitro cytotoxicity study results showed that VPDG had low toxicity to MCF-7 cells and HepG2 cells at experimental concentrations. In cell uptake experiments, VPDG could significantly increase the internalization rates (61.75%±5.22%) in VEGFR-positive HepG2 cells compared to PLL-DTPA-Gd (PDG) (25.16%±4.71%, P<0.05). In MRI studies in vitro, significantly higher T1 relaxivity (14.184 mM-1 s-1) was observed compared to Magnevist® (4.9 mM-1 s-1; P<0.01). Furthermore, in vivo MRI study results showed that VPDG could significantly enhance the tumor signal intensity and prolong the diagnostic time (from <1 h to 2.5 h). These results indicated that macromolecular VPDG was a promising MRI contrast agent and held great potential for molecular diagnosis of tumor. Keywords: MRI, contrast agent, VEGFR, biotin–avidin reaction, relaxivity
format article
author Liu YJ
Wu XY
Sun XH
Wang D
Zhong Y
Jiang DD
Wang TQ
Yu DX
Zhang N
author_facet Liu YJ
Wu XY
Sun XH
Wang D
Zhong Y
Jiang DD
Wang TQ
Yu DX
Zhang N
author_sort Liu YJ
title Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin–avidin-specific binding
title_short Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin–avidin-specific binding
title_full Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin–avidin-specific binding
title_fullStr Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin–avidin-specific binding
title_full_unstemmed Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin–avidin-specific binding
title_sort design, synthesis, and evaluation of vegfr-targeted macromolecular mri contrast agent based on biotin–avidin-specific binding
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/5cdb75c328334483a40cc6a4e1086fea
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