High-Resolution and Dynamic Visualization of Intracellular Redox Potential Using a Metal-Organic Framework-Functionalized Nanopotentiometer

Redox potential plays a key role in regulating intracellular signaling pathways, with its quantitative analysis in individual cells benefiting our understanding of the underlying mechanism in the pathophysiological events. Here, a metal organic framework (MOF)-functionalized SERS nanopotentiometer has been developed for the dynamic monitoring of intracellular redox potential. The approach is based on the encapsulation of zirconium-based MOF (Uio-66-F₄) on a surface of gold-silver nanorods (Au-Ag NRs) that is modified with the newly synthesized redox-sensitive probe ortho-mercaptohydroquinone (HQ). Thanks to size exclusion of MOF as the chemical protector, the nanopotentiometer can be adapted to long-term use and possess high anti-interference ability toward nonredox species. Combining the superior fingerprint identification of SERS with the electrochemical activity of the quinone/hydroquinone, the nanopotentiometer shows a reversible redox responsivity and can quantify redox potential with a relatively wide range of −250-100 mV. Furthermore, the nanopotentiometer allows for dynamic visualization of intracellular redox potential changes induced by drugs’ stimulation in a high-resolution manner. The developed approach would be promising for offering new insights into the correlation between redox potential and tumor proliferation-involved processes such as oxidative stress and hypoxia.