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

Abstract

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.