Photoactivated Nanowires as <i>In Situ</i> Transmembrane Electron Tunnels for Dual-Model Monitoring of Intracellular Biomarkers

The insertion of a single nanoelectrode into the cell or fluorescence detection has enabled the nondestructive tracking of intracellular biomarkers. However, the reliance on extremely expensive micromanipulators or intricate fluorescent probes has limited their widespread application. To address this challenge, we propose a novel strategy that employs modified multiwalled carbon nanotubes (MWCNTs) as artificial transmembrane electron tunnels. These MWCNTs can be spontaneously and nondestructively semiembedded within cells while exhibiting remarkable conductivity. When the photosensitive electrodes on the cell surface are illuminated, photogenerated electron-hole pairs are produced. The holes can enter the cell through the nanowires, thus promoting oxidation reactions with target molecules and generating real-time electrical signals for monitoring intracellular biomarkers. Meanwhile, the engineered recognition element on the nanowire transitions to an excited state and subsequently returns to the ground state through electrochemiluminescence (ECL), enabling <i>in situ</i> visualization of intracellular biomarkers. This groundbreaking approach not only eliminates the need for micromanipulators and fluorescent probes but also enables simultaneous electrical and optical monitoring of intracellular biomarker levels, significantly reducing false-positive risks. This innovation was validated to be feasible using NADH as an intracellular target molecule, marking a shift in intracellular sensing strategies.