Ultrasensitive Multiplex Imaging of Cell Surface Proteins via Core-Shell Surface-Enhanced Raman Scattering Nanoprobes

Cell surface proteins, as important components of biological membranes, cover a wide range of important markers of diseases and even cancers. In this regard, precise detection of their expression levels is of crucial importance for both cancer diagnosis and the development of responsive therapeutic strategies. Herein, a size-controlled core-shell Au@ Copper(II) benzene-1,3,5-tricarboxylate (Au@Cu-BTC) nanomaterial was synthesized for specific and simultaneous imaging of multiple protein expression levels on cell membranes. The porous shell of Cu-BTC constructed on Au nanoparticles enabled effective loading of Raman reporter molecules, followed by further modification of the targeting moieties, which equipped the nanoprobe with good specificity and stability. Additionally, given the flexibility of the types of Raman reporter molecules available for loading, the nanoprobes were also demonstrated with good multichannel imaging capabilities. Ultimately, the present strategy of electromagnetic and chemical dual Raman scattering enhancement was successfully applied for the simultaneous detection of varied proteins on cell surfaces with high sensitivity and accuracy. The proposed nanomaterial holds promising applications in biosensing and therapeutic fields, which could not only provide a general strategy for the synthesis of metal–organic framework-based core-shell surface-enhanced Raman scattering nanoprobes but also enable further utilization in multitarget and multichannel cell imaging.