Gold-Photodeposited Silver Nanowire Endoscopy for Cytosolic and Nuclear pH Sensing

Intracellular pH variations are a crucial indicator of physiological and pathological conditions. As such, cancer is known to have a direct interplay with pH dysregulation. For investigation of the pH alterations in cells, metal nanoparticles have been widely used as surface-enhanced Raman scattering (SERS)-based sensors thanks to their high pH sensitivity. However, these SERS probes allow for detection of the pH exclusively at the acidic compartments of the cells (endolysosomes), where particles are entrapped after their endocytosis. Consequently, the results obtained with metal nanoparticles are limited, and the relationship between the pH values detected in the cells and their physiological conditions remains unclear. Herein, we propose an alternative approach based on gold-deposited silver nanowire endoscopy to study cytosolic and nuclear pH variations with high spatiotemporal resolution and sensitivity. The sensing probe was fabricated by depositing gold nanostructures on silver nanowires (Au-dep AgNWs) via visible-laser-light irradiation and modifying the surface with a pH-responsive Raman reporter (4-mercaptobenzoic acid). The high pH sensitivity was demonstrated by immersing the probe in solutions with different pH values (4.4-9.3). The endoscopic probe was then inserted into either the nucleus or cytosol of a living HeLa cell for site-specific pH sensing. The same experiments were performed after the addition of a hypoxia mimetic agent (CoCl₂) and an anticancer drug (cisplatin), individually. Notably, our probe accurately detected specific pH variations upon these treatments over time. Similar pH alterations were not measured in untreated cells. The results reported in this work clearly show that Au-dep AgNW endoscopy is a promising powerful tool for pH-sensing applications in biological systems.