Intrinsic SERS Fingerprints of Aptamer-Peptide Conjugates for Direct High-Specific Profiling Abnormal Protein Levels in Cancer Patients

作者：Su, Mengke; Yang, Shixuan; Xu, Min; Du, Shanshan; Zheng, Liqin; Wang, Xian; Qu, Cheng; Liu, Honglin^*

来源：Analytical Chemistry, 2023, 95(33): 12398-12405.

DOI：10.1021/acs.analchem.3c01988

• RAMAN-SPECTROSCOPY
• THROMBIN
• DNA
• BLOOD

Surface-enhanced Raman spectroscopy (SERS) with ultrasensitivevibrational fingerprints enables quick identification and trace detectionof various kinds of molecules. But proteins usually have low Ramancross sections and are difficult to generate recognizable signalsin direct SERS detection. Recently, nucleic acid-peptide conjugatesare emerging with great potential in structuring, assembling, catalyzing,sensing, etc., and the coupling of aptamers further enables superiorbiological recognition and programmability. Here, we develop the aptamer-peptideconjugates as a new kind of SERS probe for direct high-specific profilingabnormal protein levels in cancer patients. The aptamer conjugatedwith glutathione (GSH) functions as both the recognition element andthe SERS reporters that can simultaneously generate SERS fingerprintsof both peptides and nucleic acids. This kind of biocompatible probeappears to have excellent performance in high-salt environments andrealizes rapid, simple, and multisignal detection of thrombin (TB).Data-driven soft independent modeling of class analogy (DD-SIMCA)is used to distinguish SERS profiles of actual blood samples and realizethe identification and classification of cancer patients. Furthermore,the effect of low-temperature storage time on blood samples is analyzedby tracking the changes of SERS profiles; the results hint that plasmasamples stored under 4 & DEG;C for more than 2 days could generatefalse negative results due to TB hydrolysis, which has important implicationsfor clinical sample analysis. This kind of nucleic acid-peptide conjugateprovides new ideas for SERS sensing strategy in the future.