Abstract

Main observation and conclusionSurface‐enhanced Raman spectroscopy (SERS)‐based bioanalytical technique involves the interaction of SERS‐active substrate with complex environment, which has aroused intensive research interests. Compared to the commonly used Au SERS substrates, Ag nanocrystals have larger optical absorption cross section and acceptable price, but they possess poor oxidation resistance and potential biotoxicity, and the occurrence of unnecessary chemical reactions is inevitable due to the direct contact with probe molecules. Herein, we report a graphene‐isolated AuAg nanocrystal (GIAAN) with the SERS‐active AuAg core confined in a nanospace of few‐layer graphene shell, which possesses unique Raman peaks, high SERS activity, excellent stability, superior fluorescence quenching performance and good biocompatibility. Based on the limited solubility of GIAAN in water and organic solvents, it is able to spontaneously generate interfacial self‐assembled GIAAN (ISA‐GIAAN) film at immiscible two‐phase interfaces without any inducer, and multiphase Raman analysis of both water‐ and lipid‐soluble drug model molecules is further achieved. Moreover, the GIAAN is further non‐covalently functionalized with polyoxyethylenestearyl ether (C18‐PEG) to acquire GIAAN@PEG with good water‐solubility for SERS quantitative analysis in homogeneous system and multimodal Raman imaging of MCF‐7 cells. We expect the versatile GIAAN holds great potential to monitor drug metabolism and guide intended drug delivery in clinic trials.

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