Introduction to the special issue on surface-enhanced Raman spectroscopy and functionalized plasmonic nanoparticles for biomedical applications

Since its first discovery in 1974 from the enhanced Raman spectra of pyridine molecules on roughened silver surface, surface-enhanced Raman spectroscopy (SERS) has garnered significant attention in the field of chemistry, biology, and medicine. With the sensitivity of down to single-molecule level and the intrinsic “fingerprint” spectrum, SERS enables the ultra-sensitive, specific, selective, and multiplexing label-free analysis of a trace of molecules in aqueous biological environments, minus the interference from water, white-light or tissue autofluorescence background. The developments on nanofabrication technology continuously facilitate the innovation on plasmonic nanoparticles (NPs), making SERS one of the fastest developing spectroscopic and analytic techniques. Furthermore, SERS nanotags, a class of Raman-encoded and biofunctionalized plasmonic NPs, have been serving as novel optical labels to expand the SERS applications from label-free sensing to the labelled diagnostics, imaging, and intraoperative Raman image-guided surgery.

We hope that the eight articles from this special issue will provide the readers the latest developments in SERS and plasmonic NPs for biomedical applications. The issue includes one review article on plasmonic NPs in targeted gene delivery, bioimaging and molecular recognition.¹ In addition, seven original research articles are presented, covering the topics of nanomaterial fabrication,^2,3,4 biomedical detection,^5,6,7 and deep optical penetration.⁸ Specifically, Duffield et al. reported the synthesis of core-shell SERS NPs with gold core, silver shell and the Raman reporter molecules in between. They determined the ideal ratio for silver nitrate to hydroquinone, the reducing agent for SERS NPs with the strong and stable Raman signal, which holds promises as the labelled diagnosis of cancer biomarkers.² Jiang et al. used Au@MIL-101(Fe) framework nanostructures as plasmonic hot spots, to conduct the trace analysis of creatinine in urine, with a limit of detection (LOD) down to 0.1$\mu$mol/L and a linear relationship in the range of 1–100$\mu$mol/L.³ Liu et al. invented the advanced Hedgehog-like SERS nanostructures for trace analysis by using self-assembled nanosphere arrays.⁴ Their SERS device reached an enhancement factor up to 10⁷, with a LOD of 10nM for thiram molecules, which is promising for the detection of toxic organic pesticides. Li et al. reported the use of dynamic SERS (D-SERS) to determine the phenotypic variations of fungal cells, assisted by machine learning methods for classification and prediction; their proposed technique holds promises for new drug screening.⁵ Hu et al. established models with testing serum SERS spectra to predict the sensitivity of docetaxel chemotherapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC).⁶ Their model achieved the accuracy of 0.73 and Area Under Curve (AUC) of 0.83. Feng et al. synthesized mitochondria-targeting Pt nanoclusters using cytochrome c aptamer (CytcApt) as templates.⁷ The obtained nanoclusters can produce OH by H₂O₂ in acidic environments to kill 4T1 tumor cells, showing excellent therapeutic potential for chemodynamic therapy. Moreover, Zhang et al. presented their investigation on micro-scale spatially offset Raman spectroscopy (SORS) probe for deep-layer SERS detections.⁸ They demonstrated the SORS probe with 2.1mm in diameter showed better tissue penetration ability than the conventional hand-held probe either on tissue phantom and ex-vivo porcine muscle, unveiling the possibility of combining the micro-SORS probe and SERS NPs for noninvasive in vivo endoscopic examination.

This issue contains the original studies ranging from SERS substrates and label-free detections to the advanced SERS detection instrumentation and data processing methods. As it provides a broad and frontier view about the recent developments in SERS field, we strongly recommend this issue. Finally, we thank all the contributing authors for making this issue possible.