Early detection of pancreatic cancers in liquid biopsies by ultrasensitive fluorescence nanobiosensors

Nanomedicine : Nanotechnology, Biology, and Medicine
Madumali KalubowilageStefan H Bossmann

Abstract

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 metalloproteinase-1, -3, and - 9, cathepsin-B and -E, urokinase plasminogen activator, and neutrophil elastase, which is a potential game-changer.

Citations

Dec 4, 2019·Current Protein & Peptide Science·Obdulia Covarrubias-ZambranoStefan H Bossmann
Nov 6, 2018·Biosensors·Sandra Lara, André Perez-Potti
Aug 8, 2021·International Journal of Molecular Sciences·Andreea NedelcuLucian Mocan

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