期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 14, 期 6, 页码 1823-1832出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2018.04.020
关键词
Nanomedicine; Nanodiagnostics; Liquid biopsy; Biophotonics; Pancreatic cancer detection; Pancreatic ductal adenocarcinoma; Sub-femtomolar limit of detection
资金
- NSF [CBET 1159966, 1337438]
- Johnson Cancer Center at Kansas State University
- Vendig Cancer Research Fund
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [1337438] Funding Source: National Science Foundation
Numerous proteases, such as matrix metalloproteinases (MMPs), cathepsins (CTS), and urokinase plasminogen activator (UpA), are dysfunctional (that is, over- or under-expressed) in solid tumors, when compared to healthy human subjects. This offers the opportunity to detect early tumors by liquid biopsies. This approach is of particular advantage for the early detection of pancreatic cancer, which is a silent killer. We have developed fluorescence nanobiosensors for ultrasensitive (sub-femtomolar) arginase and protease detection, consisting of water-dispersible Fe/Fe3O4 core/shell nanoparticles and two tethered fluorescent dyes: TCPP (Tetrakis(4-carboxyphenyl)porphyrin) and cyanine 5.5. Upon posttranslational modification or enzymatic cleavage, the fluorescence of TCPP increases, which enables the detection of proteases at sub-femtomolar activities utilizing conventional plate readers. We have identified an enzymatic signature for the detection of pancreatic adenocarcinomas in serum, consisting of arginase, matrix mctalloproteinase-1, -3, and -9, cathepsin-R and -E, urokinase plasminogen activator, and neutrophil elastase, which is a potential game-changer. (C) 2018 Elsevier Inc. All rights reserved.
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