Dye‐Sensitized Downconversion Nanoprobes with Emission Beyond 1500 Nm for Ratiometric Visualization of Cancer Redox State

Detection of glutathione (GSH) in the body is essential to accurately map the redox state of cells and real‐time visualization of physiological and pathological conditions in vivo. However, traditional fluorescence (FL) imaging in the near‐infrared I region (NIR‐I, 650–900 nm) is difficult to quantitively visualize GSH in vivo due to the tissue autofluorescence background and disastrous photon scattering. Herein, a NIR‐IIb (1500–1700 nm) nanoprobe consisting of 4‐nitrophenol‐Cy7 (NPh) conjugated lanthanide‐based downconversion nanoparticles (DCNP@NPh‐PEG) is developed for in vivo ratiometric imaging of GSH. In the presence of GSH, NPh shows responsively enhanced FL emission at 808 nm, thus enhancing FL signal at 1550 nm of DCNPs excited by 808 nm (F1550, 808Ex) through non‐radiative energy transfer (NRET) effect, while the fluorescence of DCNP at 1550 nm excited by 980 nm laser (F1550, 980Ex) is stable because no NRET occurred. The ratiometric F1550, 980Ex/F1550, 808Ex value exhibits a linearship with GSH concentration ranged from 0–24 mm with detection limit of 0.3 mm. The NIR‐IIb nanoprobe has excellent performance in detecting and imaging GSH in both subcutaneous tumor and orthotopic colon tumor in vivo with high accuracy and resolution. The design strategy of the ratiometric NIR‐II FL nanoprobe based on the activated FERT effect provides a reliable tool for the development of NIR‐II nanoprobes for accurate biosensing in vivo.