Glypican-1-antibody-conjugated Gd-Au nanoclusters for FI/MRI dual-modal targeted detection of pancreatic cancer

Xin Huang,1,* Chengqi Fan,2,* Huanhuan Zhu,1 Wenjun Le,1 Shaobin Cui,1 Xin Chen,3 Wei Li,4 Fulei Zhang,4 Yong Huang,4 Donglu Shi,1,5 Zheng Cui,1,6 Chengwei Shao,2 Bingdi Chen1 1The Institute for Translational Nanomedicine, Shanghai East Hospital, The Institute for Biomedical Engineering & N...

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Autores principales: Huang X, Fan C, Zhu H, Le W, Cui S, Chen X, Li W, Zhang F, Huang Y, Shi D, Cui Z, Shao C, Chen B
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Publicado: Dove Medical Press 2018
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spelling oai:doaj.org-article:26311c28bfc64d21b55558c14bf3258c2021-12-02T06:08:02ZGlypican-1-antibody-conjugated Gd-Au nanoclusters for FI/MRI dual-modal targeted detection of pancreatic cancer1178-2013https://doaj.org/article/26311c28bfc64d21b55558c14bf3258c2018-04-01T00:00:00Zhttps://www.dovepress.com/glypican-1-antibody-conjugated-gd-au-nanoclusters-for-fimri-dual-modal-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xin Huang,1,* Chengqi Fan,2,* Huanhuan Zhu,1 Wenjun Le,1 Shaobin Cui,1 Xin Chen,3 Wei Li,4 Fulei Zhang,4 Yong Huang,4 Donglu Shi,1,5 Zheng Cui,1,6 Chengwei Shao,2 Bingdi Chen1 1The Institute for Translational Nanomedicine, Shanghai East Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai, China; 2Radiology Department of Changhai Hospital, The Second Military Medical University, Shanghai, China; 3Department of Thyroid Surgery, The First Bethune Hospital of Jilin University, Jilin, China; 4International Joint Cancer Institute, The Second Military Medical University, Shanghai, China; 5The Materials Science & Engineering Program, Department of Mechanical & Materials Engineering, College of Engineering & Applied Science, University of Cincinnati, OH, USA; 6Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, USA *These authors contributed equally to this work Introduction: Pancreatic cancer (PC) has a poor prognosis with high mortality, due to the lack of effective early diagnostic and prognostic tools. Materials and methods: In order to target and diagnose PC, we developed a dual-modal imaging probe using Glypican-1 (GPC-1) antibody conjugated with Gd–Au nanoclusters (NCs; Gd-Au-NC-GPC-1). GPC-1 is a type of cell surface heparan sulfate proteoglycan, which is often highly expressed in PC. The probe was successfully prepared with a hydrodynamic diameter ranging from 13.5 to 24.4 nm. Results: Spectral characteristics showed absorption at 280 nm and prominent emission at 650 nm. Confocal microscopic imaging showed effective detection of GPC-1 highly expressed PC cells by Gd-Au-NC-GPC-1, which was consistent with flow cytometry results. In vitro relaxivity characterization demonstrated that the r1 value of the probe was 17.722 s−1 mM−1 Gd, which was almost 4 times higher compared with that of Gd-diethylenetriaminepentacetate (DTPA; r1 value =4.6 s−1 mM−1 Gd). Gd-Au-NC-GPC-1 exhibited similar magnetic resonance (MR) signals when compared to Gd-DTPA even at lower Gd concentrations. Much higher MR signals were registered in PC cells (COLO-357) compared with normal cells (293T). Furthermore, Gd-Au-NC-GPC-1 could effectively detect PC cells in vivo by dual-modal fluorescence imaging/magnetic resonance imaging (FI/MRI) at 30 minutes postinjection. In addition, Gd-Au-NC-GPC-1 did not show significant biotoxicity to normal cells at tested concentrations both in vitro and in vivo. Conclusion: Gd-Au-NC-GPC-1 has demonstrated to be a promising dual-modal FI/MRI contrast agent for targeted diagnosis of PC. Keywords: pancreatic cancer, Glypican-1, fluorescence imaging, magnetic resonance imaging, Gd–Au NCsHuang XFan CZhu HLe WCui SChen XLi WZhang FHuang YShi DCui ZShao CChen BDove Medical Pressarticlepancreatic cancerGlypican-1fluorescence imagingmagnetic resonance imagingGd-Au NCsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 2585-2599 (2018)
institution DOAJ
collection DOAJ
language EN
topic pancreatic cancer
Glypican-1
fluorescence imaging
magnetic resonance imaging
Gd-Au NCs
Medicine (General)
R5-920
spellingShingle pancreatic cancer
Glypican-1
fluorescence imaging
magnetic resonance imaging
Gd-Au NCs
Medicine (General)
R5-920
Huang X
Fan C
Zhu H
Le W
Cui S
Chen X
Li W
Zhang F
Huang Y
Shi D
Cui Z
Shao C
Chen B
Glypican-1-antibody-conjugated Gd-Au nanoclusters for FI/MRI dual-modal targeted detection of pancreatic cancer
description Xin Huang,1,* Chengqi Fan,2,* Huanhuan Zhu,1 Wenjun Le,1 Shaobin Cui,1 Xin Chen,3 Wei Li,4 Fulei Zhang,4 Yong Huang,4 Donglu Shi,1,5 Zheng Cui,1,6 Chengwei Shao,2 Bingdi Chen1 1The Institute for Translational Nanomedicine, Shanghai East Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai, China; 2Radiology Department of Changhai Hospital, The Second Military Medical University, Shanghai, China; 3Department of Thyroid Surgery, The First Bethune Hospital of Jilin University, Jilin, China; 4International Joint Cancer Institute, The Second Military Medical University, Shanghai, China; 5The Materials Science & Engineering Program, Department of Mechanical & Materials Engineering, College of Engineering & Applied Science, University of Cincinnati, OH, USA; 6Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, USA *These authors contributed equally to this work Introduction: Pancreatic cancer (PC) has a poor prognosis with high mortality, due to the lack of effective early diagnostic and prognostic tools. Materials and methods: In order to target and diagnose PC, we developed a dual-modal imaging probe using Glypican-1 (GPC-1) antibody conjugated with Gd–Au nanoclusters (NCs; Gd-Au-NC-GPC-1). GPC-1 is a type of cell surface heparan sulfate proteoglycan, which is often highly expressed in PC. The probe was successfully prepared with a hydrodynamic diameter ranging from 13.5 to 24.4 nm. Results: Spectral characteristics showed absorption at 280 nm and prominent emission at 650 nm. Confocal microscopic imaging showed effective detection of GPC-1 highly expressed PC cells by Gd-Au-NC-GPC-1, which was consistent with flow cytometry results. In vitro relaxivity characterization demonstrated that the r1 value of the probe was 17.722 s−1 mM−1 Gd, which was almost 4 times higher compared with that of Gd-diethylenetriaminepentacetate (DTPA; r1 value =4.6 s−1 mM−1 Gd). Gd-Au-NC-GPC-1 exhibited similar magnetic resonance (MR) signals when compared to Gd-DTPA even at lower Gd concentrations. Much higher MR signals were registered in PC cells (COLO-357) compared with normal cells (293T). Furthermore, Gd-Au-NC-GPC-1 could effectively detect PC cells in vivo by dual-modal fluorescence imaging/magnetic resonance imaging (FI/MRI) at 30 minutes postinjection. In addition, Gd-Au-NC-GPC-1 did not show significant biotoxicity to normal cells at tested concentrations both in vitro and in vivo. Conclusion: Gd-Au-NC-GPC-1 has demonstrated to be a promising dual-modal FI/MRI contrast agent for targeted diagnosis of PC. Keywords: pancreatic cancer, Glypican-1, fluorescence imaging, magnetic resonance imaging, Gd–Au NCs
format article
author Huang X
Fan C
Zhu H
Le W
Cui S
Chen X
Li W
Zhang F
Huang Y
Shi D
Cui Z
Shao C
Chen B
author_facet Huang X
Fan C
Zhu H
Le W
Cui S
Chen X
Li W
Zhang F
Huang Y
Shi D
Cui Z
Shao C
Chen B
author_sort Huang X
title Glypican-1-antibody-conjugated Gd-Au nanoclusters for FI/MRI dual-modal targeted detection of pancreatic cancer
title_short Glypican-1-antibody-conjugated Gd-Au nanoclusters for FI/MRI dual-modal targeted detection of pancreatic cancer
title_full Glypican-1-antibody-conjugated Gd-Au nanoclusters for FI/MRI dual-modal targeted detection of pancreatic cancer
title_fullStr Glypican-1-antibody-conjugated Gd-Au nanoclusters for FI/MRI dual-modal targeted detection of pancreatic cancer
title_full_unstemmed Glypican-1-antibody-conjugated Gd-Au nanoclusters for FI/MRI dual-modal targeted detection of pancreatic cancer
title_sort glypican-1-antibody-conjugated gd-au nanoclusters for fi/mri dual-modal targeted detection of pancreatic cancer
publisher Dove Medical Press
publishDate 2018
url https://doaj.org/article/26311c28bfc64d21b55558c14bf3258c
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