Extending Hypochlorite Sensing from Cells to Elesclomol-Treated Tumors in Vivo by Using a Near-Infrared Dual-Phosphorescent Nanoprobe.

Reactive oxygen species (ROS), when beyond the threshold, can exhaust capacity of cellular antioxidant and ultimately trigger cell apoptosis in tumor biology. However, the roles of hypochlorite (ClO-) in this process are much less clear compared with her ROS, and its detection is easily obstructed by tissue penetration and endogenous fluorophores. Herein, we first synthesized a near-infrared (NIR) ratiometric ClO- probe (Ir NPs) comprising two kinds of phosphorescent iridium(III) complexes (Ir1 and Ir2), encapsulated with amphiphilic DSPE-mPEG5000. Ir NPs is dual-emissive and shows obvious changes in phosphorescence intensity ratios and lifetimes of two emission bands upon exposure to ClO-. During the ClO- detection, ratiometric photoluminescence imaging is much more reliable over intensity-based one for its self-calibration, while time-resolved photoluminescence imaging (TRPI) could distinguish the phosphorescence with long lifetime of Ir NPs from short-lived autofluorescence of tissues, meaning high accuracy of ClO- determination. With NIR emission, long phosphorescence lifetime, fast response and excellent biocompatibility, Ir NPs was applied to detecting ClO- in vitro and in vivo by means of ratiometric phosphorescence imaging and TRPI with high signal-to noise-ratio (SNR). Importantly, we demonstrated the elevated ClO- in elesclomol-stimulated tumors in living mice for the first time, which holds great potentials to visualize the boost of ClO- in anticarcinogen-treated tumors and further investigate ROS-related oncotherapeutics.