期刊
INTERNATIONAL JOURNAL OF NANOMEDICINE
卷 13, 期 -, 页码 2585-2599出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S158559
关键词
pancreatic cancer; Glypican-1; fluorescence imaging; magnetic resonance imaging; Gd-Au NCs
资金
- Natural Science Foundation of China [81772285, 31671029]
- Shanghai Health and Family Planning Commission Project [2017YQ051]
- Shanghai Science and Technology Commission Project [17411968700]
- Shanghai Natural Science Foundation [16ZR1400700]
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-NCGPC-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.
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