SERS-Based AND Logic Gate for Monitoring Signal Transduction of Specific Cancer Cells and Evaluating Antitumor Efficacy via Imaging of Membrane Protein Dimerization

The abnormal sustained activation of mesenchymal-epithelial transition factor (Met) dimers on cancer cell membranes is closely associated with malignant tumor progression; however, accurate identification of specific cancer cells and subsequent sensitive monitoring of intercellular signaling pathways activated by membrane Met dimerization within the intricate tumor microenvironments remain significant challenges. Here, an innovative surface-enhanced Raman scattering (SERS)-based AND logic gate was proposed for the highly sensitive imaging of Met protein dimers on target cancer cells, facilitated through the assembly of recognition probes (RPs) and SERS tag network nanostructures (RP-SERS tag NWs) with rich SERS hot spots. The SERS-based AND logic gate, powered by the synergistic interplay of aptamer-targeted cancer cell-triggered localized catalytic hairpin assembly (LCHA) and proximity ligation-induced DNAzyme cleavage, achieves precise identification of specific tumor cells and real-time imaging of membrane Met protein dimerization. Moreover, we successfully employed SERS imaging to visualize the HGF/Met signaling pathway between stromal cells or stem cells and cancer cells within the natural complexity of cellular microenvironments. This approach also allows for real-time evaluation of the antitumor efficacy of drugs targeting receptor dimerization. These results indicated that the proposed AND logic-based SERS strategy holds promise for advancing cancer diagnostics, understanding cellular communication mechanisms, and accelerating the development of more effective therapeutic interventions.