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

Abstract

IntroductionPancreatic cancer (PC) has a poor prognosis with high mortality, due to the lack of effective early diagnostic and prognostic tools.Materials and methodsIn 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.ResultsSpectral 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.ConclusionGd-Au-NC-GPC-1 has demonstrated to be a promising dual-modal FI/MRI contrast agent for targeted diagnosis of PC.

11g, a Potent Antifungal Candidate, Enhances Candida albicans Immunogenicity by Unmasking β-Glucan in Fungal Cell Wall

“…For cytotoxicity assay, rat cardiac myocytes (H9C2; 8 × 10 3 cells/well) were cultured in 96-well plates and incubated in DMEM (HyClone, Logan City, United States), supplemented with 10% FBS at 37 • C in the presence of 5% CO 2 . The following day, a CCK-8 assay was performed, as described previously (Huang et al, 2018). Briefly, H9C2 were incubated in DMEM with or without 11g at 37 • C for 24 h. After discarding medium with 11g, washing cells two times with PBS, and adding fresh medium with CCK-8 solution, cells were further incubated at 37 • C for 1 h. Absorbance at 450 nm was measured by ELISA Plate Reader (Thermo Scientific).…”

Current status of targeted microbubbles in diagnostic molecular imaging of pancreatic cancer

“…Numerous rodent models have contributed to the understanding of PDAC pathogenesis and thereby, provided opportunities to characterize and detect disease progression from benign to malignant stages with imaging tools. AsPC-1, 105,115 BxPC-3, 47,92,113 Capan-1, 117 Capan-2, 102,110,120 COLO-357, 94,97 MIA PaCa-2, 74,106 Panc-1 95,129 and PL45 cells 108 (KPC) 89,124 and Pdx-1-Cre; LSL-Kras G12D/+ ; Ink4a/Arf −/− . 16,[71][72][73]104 Last mentioned model has been utilized in molecular ultrasound imaging due to the expression of Thy1 or VEGFR2 on its tumor neovasculature.…”

Targeting Glycans and Heavily Glycosylated Proteins for Tumor Imaging

“…In cancer, aberrant glycosylation is mainly characterized by increased N -glycan branching, augmented O -glycan density, incomplete glycan synthesis, and, in more advanced cancers, synthesis of neo-glycan determinants that carry large amounts of sialic acids or fucose residues [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61...…”

“…Over 70% of HCC cases express high levels of glypican-3, while expression is absent on benign hepatic lesions and normal liver tissue [ 136 , 140 , 141 ]. A vast number of studies evaluated glypican-3 as a PET, ultrasound (US), NIR, and MR imaging target for HCC using several targeting moieties and conjugates of a different origin [ 40 , 41 , 42 , 43 , 44 , 142 ]. In all in vivo studies, HepG2 cells could be clearly localized and delineated using a glypican-3-specific tracer.…”