Surface-Roughened SERS-Active Single Silver Nanowire for Simultaneous Detection of Intracellular and Extracellular...

The simultaneous and accurate detection of intracellular pH (pH_i) and extracellular pH (pH_e) is essential for studying the complex physiological activities of cancer cells and exploring pH-related therapeutic mechanisms. Here, we developed a super-long silver nanowire-based surface-enhanced Raman scattering (SERS) detection strategy for simultaneous sensing of pH_i and pH_e. A surface-roughened silver nanowire (AgNW) with a high aspect ratio is prepared at a nanoelectrode tip using a Cu-mediated oxidation process, which is then modified by pH-sensitive 4-mercaptobenzoic acid (4-MBA) to form 4-MBA@AgNW as a pH sensing probe. With the assistance of a 4D microcontroller, 4-MBA@AgNW is efficient in simultaneously detecting pH_i and pH_e in both 2D and 3D culture cancer cells by SERS, with minimal invasiveness, high sensitivity, and spatial resolution. Further investigation proves that the surface-roughened single AgNW can also be used in monitoring the dynamic variation of pH_i and pH_e of cancer cells upon stimulation with anticancer drugs or under a hypoxic environment.