BackgroundGlypican-1 (GPC1) is expressed in pancreatic ductal adenocarcinoma (PDAC) cells and adjacent stromal fibroblasts. Recently, GPC1 circulating exosomes (crExos) have been shown to be able to detect early stages of PDAC. In this study, we investigated the usefulness of crExos GPC1 as a biomarker for PDAC.MethodsPlasma was obtained from patients with benign pancreatic disease (n = 16) and PDAC (n = 27) prior to pancreatectomy, and crExos were isolated by ultra-centrifugation. Protein was extracted from surgical specimens (adjacent normal pancreas, n = 13; and PDAC, n = 17). GPC1 levels were measured using enzyme-linked immunosorbent assay (ELISA).ResultsThere was no significant difference in GPC1 levels between normal pancreas and PDAC tissues. This was also true when comparing matched pairs. However, GPC1 levels were enriched in PDAC crExos (n = 11), compared to the source tumors (n = 11; 97 ± 54 vs. 20.9 ± 12.3 pg/mL; P < 0.001). In addition, PDACs with high GPC1 expression tended to have crExos with higher GPC1 levels. Despite these findings, we were unable to distinguish PDAC from benign pancreatic disease using crExos GPC1 levels. Interestingly, we found that in matched pre and post-operative plasma samples there was a significant drop in crExos GPC1 levels after surgical resection for PDAC (n = 11 vs. 11; 97 ± 54 vs. 77.8 ± 32.4 pg/mL; P = 0.0428). Furthermore, we found that patients with high crExos GPC1 levels have significantly larger PDACs (>4 cm; P = 0.012).ConclusionsHigh GPC1 crExos may be able to determine PDAC tumor size and disease burden. However, further efforts are needed to elucidate its role as a diagnostic and/or prognostic biomarker using larger cohorts of PDAC patients.

Gold nanostars; self-assembled monolayers; near infrared; NIR-II; metal enhanced fluorescence; localized surface plasmon resonance; fluorescence lifetime.Gold nanostars (AuNS) are receiving increasing attention for their potential applications in bionanotechnology, because of their unique optical properties related to their complex branched morphology. 1 2 3 4 5 6 7 8 9 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 2 confirming that AuNS substrates are promising NIR-MEF platforms for the development of ultrasensitive biosensing applications. Using fluorescence lifetime measurements to semi-quantitatively deconvolute the excitation enhancement from emission enhancement, as well as modelling to simulate the electric field enhancement, we show that a combination of enhanced excitation and an increased radiative decay rate, accompanied by an increase to the quantum yield, contribute to the observed large enhancement. AuNS with different morphological features exhibit significantly different excitation enhancement, indicating the important role of particle morphology on the magnitude of electromagnetic field enhancement, and the resulting enhancement factor. Importantly, enhancement factors of up to 50 times are also achieved in the NIR-II region, suggesting that this system holds promise for the future development of bright probes for NIR/NIR-II biosensing and bioimaging.

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