Activatable NIR-II ratiometric fluorescence nanoprobe for in vivo real-time dynamic imaging of GSH and its-associated diseases

Glutathione (GSH) as an important endogenous antioxidant plays key role in maintaining the intracellular redox homeostasis and the imbalance of GSH level in cells is highly implicated in many diseases such as liver damage, cancer etc. Therefore, developing GSH intelligent responsive nanoprobes for in situ monitoring of GSH level in vivo is highly essential for understanding the physiological and pathological processes. Herein, a novel GSH responsive second near-infrared (NIR-II, 1000–1700 nm) ratiometric fluorescence probe was successfully designed using lanthanide down-shifting nanoparticles NaLuF4:Yb/Er@NaLuF4@mSiO2 (DCMS) loaded with Pb(BO2)2 and GSH activated H2S donor diallyl trisulfide (DATS) for real-time monitoring of GSH level in vivo. The designed nanoprobes were converted to NaLuF4:Yb/Er@NaLuF4@mSiO2@PbS by GSH triggered cascade in-situ sulfuration reaction, resulting in turn-on orthogonal NIR-II emissions at 1260 and 1525 nm excited by 808/980 nm laser. And highly sensitive and specific detection of GSH with detection limit of 67 nM was achieved. More importantly, highly accurate and specific ratiometric imaging (F1260 nm Ex808 nm/F1525 nm Ex980 nm) of GSH in both acute alcoholic liver injury and breast tumor with aberrant expression of GSH is successfully achieved. Notably, the ratiometric value is linearly correlated with the GSH level. Thus, the designed GSH-activated NIR-II ratiometric probe provides a new strategy for real-time noninvasive monitoring of GSH level in vivo with high sensitivity and specificity.