基质金属蛋白酶-9 (MMP-9) 是一种蛋白水解酶，可降解细胞外基质并在细胞通讯中发挥关键作用。然而，在细胞间通信过程中实时监测细胞分泌的 MMP-9 仍然是一个挑战。在此，我们开发了一种基于细胞的膜锚定表面增强拉曼散射（SERS）生物传感器，使用Au@4-巯基苯甲腈（4-MBN）@Ag@肽纳米探针来监测细胞通信过程中细胞分泌的MMP-9 。该多功能纳米探针采用 Au@4-MBN@Ag 作为无干扰的 SERS 底物，具有高度增强作用，其中肽不仅可以锚定细胞膜，还可以提供 MMP-9 可激活的裂解肽链。 MMP-9介导的裂解导致Au@4-MBN@Ag纳米粒子从细胞膜上脱离，从而减少癌细胞的SERS信号。细胞膜锚定的SERS生物传感器能够在MCF-7和HUVEC细胞相互作用过程中实时监测细胞分泌的MMP-9。本研究成功展示了MCF-7细胞与HUVEC细胞通讯过程中细胞分泌的MMP-9的动态变化。所提出的纳米探针还用于精确评估乳腺癌和肝癌细胞的侵袭性。这项研究提供了一种实时监测细胞通讯过程中MMP-9分泌的新策略，这对于研究不同肿瘤过程的机制具有广阔的前景。

Matrix metalloproteinase-9 (MMP-9), a proteolytic enzyme, degrades the extracellular matrix and plays a key role in cell communication. However, the real-time monitoring of cell-secreted MMP-9 during cell-cell communication remains a challenge. Herein, we developed a cell-based membrane-anchored surface-enhanced Raman scattering (SERS) biosensor using a Au@4-mercaptobenzonitrile (4-MBN) @Ag@peptide nanoprobe for the monitoring of cell-secreted MMP-9 during cell communication. The multifunctional nanoprobe was created with Au@4-MBN@Ag acting as an interference-free SERS substrate with high enhancement in which the peptide not only serves to anchor the cell membrane but also provides MMP-9-activatable cleaved peptide chains. MMP-9-mediated cleavage resulted in the detachment of the Au@4-MBN@Ag nanoparticles from the cell membrane, thereby decreasing the SERS signals of cancer cells. The cell membrane-anchored SERS biosensor enables the real-time monitoring of cell-secreted MMP-9 during the interaction of MCF-7 and HUVEC cells. This study successfully demonstrates the dynamic change of cell-secreted MMP-9 during the communication between MCF-7 cells and HUVEC cells. The proposed nanoprobe was also utilized to precisely evaluate the breast and hepatoma cancer cell aggressiveness. This study provides a novel strategy for real-time monitoring of MMP-9 secretion during cell communication, which is promising for the investigation of the mechanisms underlying different tumor processes.