Glypican-1-antibody-conjugated Gd-Au nanoclusters for FI/MRI dual-modal targeted detection of pancreatic cancer
Received 30 November 2017
Accepted for publication 16 March 2018
Published 30 April 2018 Volume 2018:13 Pages 2585—2599
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Jiang Yang
Peer reviewer comments 2
Editor who approved publication: Dr Linlin Sun
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
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