Hybrid Quatsome‐Encapsulated Silver Nanoparticles as Stable Plasmonic Substrates for Surface‐Enhanced Raman Scattering

Surface‐enhanced Raman scattering (SERS) has emerged as a powerful spectroscopic technique for probing molecular structures and dynamics with very high sensitivity. Despite its potential, the practical implementation of SERS in biology and medicine is often hindered by the poor stability and limited biocompatibility of colloidal metal nanoparticles. In this study, we report the encapsulation of silver nanoparticles within quatsome membranes composed of cetyltrimethylammonium bromide and cholesterol, resulting in hybrid nanostructures that act as robust and efficient SERS platforms. These quatsome‐encapsulated silver nanoparticles (Q‐AgNP‐cit) exhibit prolonged colloidal stability and maintain their plasmonic properties over at least 165 days stored at 4°C, effectively minimizing nanoparticle aggregation. Using these stabilized Q‐AgNP‐cit, we explored the SERS response of two precursors of fluorescent probes, pyrene and Prodan, commonly used in lipid membrane studies due to their sensitivity to microenvironmental polarity. We first characterized the normal Raman and SERS spectra of Prodan using uncoated silver nanoparticles. The results suggest that Prodan adopts a tilted orientation on the silver surface with the nitrogen atom acting as the primary coordination site. We demonstrated that Q‐AgNP‐cit act as efficient SERS‐active substrates, as the quatsome membranes effectively confine pyrene and Prodan within a few nanometers of the metallic surface. This spatial confinement enables strong Raman signal enhancement via the electromagnetic mechanism, without the need for any external aggregating agent. The results highlight the effectiveness of Q‐AgNP‐cit combining the high sensitivity of SERS with enhanced structural stability, providing a biomimetic platform for plasmonic studies in biochemical and biomedical applications.