Simultaneous Detection and Inhibition of VCAM-1 mRNA Expression in Macrophages via Ratiometric SERS Nanoprobes

Vascular cell adhesion molecule-1 (VCAM-1) palys a key role in the occurrence and development of atherosclerosis (AS), making the monitoring and modulation of VCAM-1 expression critical for its diagnosis and treatment. To detect low-abundance VCAM-1 mRNA within macrophages, we have developed a highly sensitive ratiometric surface-enhanced Raman scattering (SERS) nanoprobe for the simultaneous precise detection and effective inhibition of VCAM-1 expression. This nanoprobe featured an Au-Au core-shell structure with dual functional layers: an interstitial 4-mercaptobenzonitrile (4-MBN) internal standard and an outer VCAM-1 mRNA recognition sequence tagged with Cy5. When the target mRNA bonded, it induced the formation of a stable duplex, distancing Cy5 from the metal surface and reducing its SERS intensity. While the shielded 4-MBN maintained a stable SERS signal. Therefore, the ultrasensitive detection of VCAM-1 mRNA within macrophages can be achieved by monitoring the proportional SERS signals of Cy5 and 4-MBN. Crucially, the binding event simultaneously suppressed VCAM-1 expression, enabling integrated diagnosis and pathological mitigation of AS. Under lipopolysaccharide (LPS)-induced pathological states, the nanoprobe dynamically tracked intracellular VCAM-1 mRNA levels while inhibiting mRNA/protein expression. This dual action blocked macrophage pyroptosis and attenuated inflammatory cytokine release, demonstrating therapeutic potential against AS progression. The ratiometric SERS nanoprobe design offers a versatile platform for nucleic acid-targeted theranostics in chronic diseases.