Early detection of pancreatic cancers in liquid biopsies by ultrasensitive fluorescence nanobiosensors
Early detection of pancreatic cancers in liquid biopsies by ultrasensitive fluorescence nanobiosensors
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DOI：
10.1016/j.nano.2018.04.020
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发表时间：
2018-08-01
影响因子：
5.4
通讯作者：
Bossmann, Stefan H.
中科院分区：
文献类型：
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作者：
Kalubowilage, Madumali;Covarrubias-Zambrano, Obdulia;Bossmann, Stefan H.
与健康人受试者相比，许多蛋白酶，如基质金属蛋白酶（MMP）、组织蛋白酶（CTS）和尿激酶纤溶酶原激活剂（UpA）在实体瘤中功能失调（即过度表达或表达不足）。这为通过液体活检检测早期肿瘤提供了机会。这种方法对于胰腺癌的早期检测特别有利，胰腺癌是一种“沉默的杀手”。我们已经开发了用于超灵敏（亚飞摩尔）酶和蛋白酶检测的荧光纳米生物传感器，由水分散性Fe/Fe 3 O 4核/壳纳米颗粒和两种拴系荧光染料组成：TCPP（四（4-羧基苯基）卟啉）和花青5.5。在翻译后修饰或酶裂解后，TCPP的荧光增加，这使得能够利用常规读板仪检测亚飞摩尔活性的蛋白酶。我们已经确定了一种用于检测血清中胰腺癌的酶标记，包括胰蛋白酶、基质金属蛋白酶-1、-3和-9、组织蛋白酶-R和-E、尿激酶纤溶酶原激活剂和中性粒细胞弹性蛋白酶，这是一种潜在的游戏规则改变者。(C)2018爱思唯尔公司All rights reserved.
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.