Construction of a magnetic-fluorescent-plasmonic nanosensor for the determination of MMP-2 activity based on SERS-fluorescence dual-mode signals

Lin Liu; Hongyu Chu; Jukun Yang; Ying Sun; Pinyi Ma; Daqian Song

doi:10.1016/j.bios.2022.114389

Construction of a magnetic-fluorescent-plasmonic nanosensor for the determination of MMP-2 activity based on SERS-fluorescence dual-mode signals

Biosens Bioelectron. 2022 Sep 15:212:114389. doi: 10.1016/j.bios.2022.114389. Epub 2022 May 20.

Authors

Lin Liu¹, Hongyu Chu², Jukun Yang¹, Ying Sun¹, Pinyi Ma³, Daqian Song⁴

Affiliations

¹ College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Qianjin Street 2699, Changchun, 130012, China.
² Nanomedicine Translational Research Center, China-Japan Union Hospital of Jilin University, Sendai Street 126, Changchun, 130033, China.
³ College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Qianjin Street 2699, Changchun, 130012, China. Electronic address: mapinyi@jlu.edu.cn.
⁴ College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Qianjin Street 2699, Changchun, 130012, China. Electronic address: songdq@jlu.edu.cn.

PMID: 35635973
DOI: 10.1016/j.bios.2022.114389

Abstract

Matrix metalloproteinase 2 (MMP-2) is a crucial biomarker of tumor growth, invasion and metastasis. In the present study, a core-satellite magnetic-fluorescent-plasmonic nanosensor (FMNS@Au) was constructed through biological self-assembly to generate localized SERS "hot spots" and an efficient FRET system for the sensitive determination of MMP-2 activity in a SERS-fluorescence dual-mode assay. In this hybrid nanosensor, a biotin-labeled peptide containing a specific MMP-2 substrate (PLGVR) was employed as a bridge for the assembly of gold nanoparticles (AuNPs) and avidin functionalized fluorescent-magnetic nanospheres (FMNS). The modified RB on FMNS served as a Raman reporter and a donor of FRET, while the AuNPs assembled on FMNS acted as SERS substrates and acceptors of FRET. In the presence of MMP-2, the SERS "hot spot" effect was weakened and the FRET system was disrupted through enzymatic cleavage of PLGVR, resulting in a reduction of SERS signal and the recovery of fluorescence emission. Importantly, this combination of SERS and fluorescence assay methods in the dual-mode nanosensor broadened the detection range for MMP-2 to 1-200 ng mL^-1, with a limit of detection of 0.35 ng mL^-1 and a limit of quantitation of 1.17 ng mL^-1. In addition, our novel nanosensor affords semi-quantitative sensing of MMP-2 by naked-eye observation and accurate detection of MMP-2 through dual-mode analysis. The practicality of FMNS@Au was validated by determination of MMP-2 activity in cell secretions and human serum samples. The designed FMNS@Au nanosensor holds great potential for clinical diagnosis of protease-related diseases.

Keywords: Dual-mode assay; Fluorescence; Magnetic-fluorescent-plasmonic nanosensor; Matrix metalloproteinase 2; Surface-enhanced Raman spectroscopy.

MeSH terms

Biosensing Techniques* / methods
Gold
Humans
Limit of Detection
Matrix Metalloproteinase 2
Metal Nanoparticles*
Spectrum Analysis, Raman / methods

Substances

Gold
Matrix Metalloproteinase 2