A multi-functional core-shell surface-enhanced Raman scattering nanosensor for simultaneous imaging of epidermal growth factor receptor on cell membranes and ROS secreted from living cells

The visualization of the substances on cell surface is an urgent need for the monitoring of signal transduction during intercellular communication and cancer diagnosis. Herein, a core-shell surface-enhanced Raman scattering (SERS) nanosensor is proposed for simultaneous imaging of epidermal growth factor receptor (EGFR) on cell membranes and reactive oxygen species (ROS) released from living cells. The SERS nanosensors are fabricated by embedding 4-mercaptobenzonitrile (4-MBN) molecules as a SERS tag for EGFR expression into the core-shell AuNPs@Au nanoparticles to form AuNPs@4-MBN@Au and further modifying the EGFR aptamers as EGFR recognition units and 2-mercaptohydroquinone (2-MHQ) as ROS responsive molecules on the surface of AuNPs@4-MBN@Au. Due to the specific interactions and narrow SERS peaks for spectral multiplexing, the nanosensors can target EGFR on cell membranes and achieve the SERS visualization of EGFR and ROS released from the living cells. Moreover, a positive relationship between EGFR and ROS levels on the cell membranes is revealed by using the nanosensors, showing that ROS can promote the expression of EGFR and that the high-level EGFR can facilitate the ROS generation. This ROS-promoted EGFR expression is further corroborated by western blot analysis. Overall, the proposed SERS strategy could provide a powerful tool to monitor the dynamic changes of EGFR and ROS and related signal transduction.