Abstract

Profiling cellular biomarkers without the interference of endogenous signals could facilitate the investigation of complex intracellular biological events and provide new possibilities for precision disease diagnosis. Herein, a surface-enhanced Raman scattering (SERS) probe with a high signal-to-background ratio (SBR) for cellular biomarker imaging is constructed. The probes are prepared by incorporating Prussian blue (PB) with porous gold nanoparticles (p-Au NPs). Due to their rich built-in Raman hotspots, the p-Au NPs are excellent SERS substrates that can significantly amplify the signals of the incorporated PB. In parallel, PB shows a single peak in the cellular silent region, where the signals from the probes and endogenous molecules can be completely resolved without the need of complex spectral unmixing. As a consequence, the combination of probe signal enhancement and background elimination endows the SERS probes with an extremely high SBR. To evaluate their performance in biomarker imaging, the high-SBR SERS probes are utilized to profile folic acids at a single-cell level. This background-free, high-precision imaging technique is conducive to early diagnosis and therapeutic response of cancer that is of great importance in clinical settings.

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