Guo Wenfei, Gao Xiaonan, Zhan Renhui, Zhao Zengteng, Xu Kehua, Tang Bo
College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Molecular and Nano Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Shandong Normal University, Jinan, 250014, PR China.
College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Molecular and Nano Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Shandong Normal University, Jinan, 250014, PR China; Medicine & Pharmacy Research Center, Binzhou Medical University, Shandong, Yantai, 264003, PR China.
Talanta. 2021 Jan 15;222:121525. doi: 10.1016/j.talanta.2020.121525. Epub 2020 Aug 11.
The expression levels of matrix metalloproteinases (MMPs) are closely related to the degree of inflammation which facilitates tumor cells' invasion and migration. A tricolor fluorescence nanoprobe based on high-fidelity gold-selenium (Au-Se) nanoplatform was designed and constructed for simultaneously imaging matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-7 (MMP-7) and matrix metalloproteinase-9 (MMP-9) to thoroughly investigate the tumor cells' invasion and migration behaviors under inflammation environment. The nanoprobe was assembled by attaching Au NPs with three different peptide substrates respectively labeled with fluorescein isothiocyanate (FITC), 5-carboxytetramethylrhodamine (5-TAMRA) and cyanine 5 (Cy5) via the Au-Se bond. The nanoprobe can specifically respond to MMP-2/7/9, thereby triggering the fluorophores' fluorescence that quenched previously by fluorescence resonance energy transfer (FRET) to realize the MMP-2/7/9's visualization in biological systems. Moreover, as the inflammation stimulated by different concentrations lipopolysaccharide (LPS), the expression of MMP-2/7/9 in SMMC-7721 cells was observed to be significantly enhanced by confocal laser scanning microscope (CLSM) imaging, and inflammation was further proved to intensify SMMC-7721 cells' invasion and migration by transwell invasion and migration experiments. Therefore, the nanoprobe can be used to monitor biomarkers to provide a visual system for the degree of invasion and migration of tumor cells in an inflammatory environment, and also offer a new strategy for the study of the correlation between various active biomacromolecules and specific intracellular pathways in cells.
基质金属蛋白酶（MMPs）的表达水平与促进肿瘤细胞侵袭和迁移的炎症程度密切相关。设计并构建了一种基于高保真金硒（Au-Se）纳米平台的三色荧光纳米探针，用于同时成像基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-7（MMP-7）和基质金属蛋白酶-9（MMP-9），以深入研究炎症环境下肿瘤细胞的侵袭和迁移行为。该纳米探针通过金硒键将分别标记有异硫氰酸荧光素（FITC）、5-羧基四甲基罗丹明（5-TAMRA）和花青素5（Cy5）的三种不同肽底物连接到金纳米颗粒上组装而成。该纳米探针可以特异性地响应MMP-2/7/9，从而触发之前通过荧光共振能量转移（FRET）淬灭的荧光团的荧光，以实现生物系统中MMP-2/7/9的可视化。此外，通过共聚焦激光扫描显微镜（CLSM）成像观察到，随着不同浓度脂多糖（LPS）刺激炎症，SMMC-7721细胞中MMP-2/7/9的表达显著增强，并且通过Transwell侵袭和迁移实验进一步证明炎症会加剧SMMC-7721细胞的侵袭和迁移。因此，该纳米探针可用于监测生物标志物，为炎症环境下肿瘤细胞的侵袭和迁移程度提供可视化系统，也为研究细胞内各种活性生物大分子与特定细胞内途径之间的相关性提供了新策略。
