Journal
ANALYTICAL CHEMISTRY
Volume 92, Issue 8, Pages 5910-5920Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.9b05837
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Funding
- NSFC [21605049, 21827814, 21974049]
- Program of Shanghai Subject Chief Scientist [15XD1501600]
- Innovation Program of Shanghai Municipal Education Commission [201701070005E00020]
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The aggregation of A beta has been reported to closely correlate with Alzheimer's disease (AD). However, clear monitoring of the entire aggregation process of A beta from monomer to fibril has been scarcely reported until now. Herein, we developed a label-free ratiometric surface enhanced Raman spectroscopic (SERS) platform for real-time monitoring of the entire process of A beta aggregation in neurons and brain tissues. Different gold nano-particles, generated in situ with A beta monomer and fibril as templates separately, were served as effective SERS substrates to achieve a high sensitivity with a limit of detection (LOD) down to 70 +/- 4 pM and 3.0 +/- 0.5 pM for A beta(40) monomer and fibrils, respectively. Besides, the introduction of ratiometric determination of A beta monomer and fibril (I-1244/I-1268) realized real-time monitoring of the entire aggregation process of A beta monomer with high accuracy and selectivity against other proteins and amino acids. The significant analytical performance of the developed platform, together with good biocompatibility, long-term stability, and remarkable spatial resolution, enabled the present SERS platform imaging and real-time monitoring and imaging of A beta aggregation influenced by different metal ions (Cu2+, Zn2+, and Fe3+) in neurons and brain tissues at the single cell level. Our results suggested that Cu2+ and Zn2+ ion of low concentration (10 mu M) promoted fibril formation, while Fe3+ and Zn2+ of high concentration (100 mu M) showed inhibition of fibrosis.
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