Reactive oxygen species (ROS), when beyond the threshold, can exhaust the capacity of cellular antioxidants and ultimately trigger cell apoptosis in tumor biology. However, the roles of hypochlorite (ClO-) in this process are much less clear compared with those of 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 NP) composed of two kinds of phosphorescent iridium(III) complexes (Ir1 and Ir2) encapsulated with amphiphilic DSPE-mPEG5000. Ir NPs are dual-emissive and show 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 the 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, resulting in the high accuracy of ClO- determination. With NIR emission, a long phosphorescence lifetime, fast response, and excellent biocompatibility, Ir NPs were applied to the detection of ClO- in vitro and in vivo by means of ratiometric phosphorescence imaging and TRPI with high signal-to noise-ratios (SNR). Importantly, we demonstrated the elevated ClO- in elesclomol-stimulated tumors in living mice for the first time, which holds great potential for the visualization of the boost of ClO- in anti-carcinogen-treated tumors and the further investigation of ROS-related oncotherapeutics.
Keywords: dual-phosphorescent nanoprobe; elesclomol-treated tumors; hypochlorite; iridium(III) complexes; near-infrared emission.