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Lysosome-targeted sequential dual-activatable NIR fluorescent probe for imaging HClO and viscosity in acute kidney
Bangyu Zou1, Jingcan Qin2, Ming Yang2
1Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, 200433, PR China.
Background:
Acute kidney injury (AKI) is a common condition among hospitalized patients, with high morbidity and mortality. Accumulating evidence suggests that hypochlorous acid (HClO)/viscosity in lysosome is closely associated with the progression of AKI, with their abnormal levels emerging as promising biomarkers for AKI. Near-infrared (NIR) fluorescent probes hold potential for tracking changes in HClO and viscosity, whereas the previous single-response/dual-channel fluorescent probes (HClO or/and viscosity) are prone to false-positive signals in biological environments, thereby compromising diagnostic accuracy. Therefore, it is of great significance to develop a lysosome-targeted sequential dual-activatable NIR fluorescent probe for imaging HClO and viscosity.
Results:
We present a lysosome-targeted NIR fluorescent probe (LNX-HClO), which operates through a sequential dual-activation mechanism requiring the simultaneous presence of elevated HClO levels and increased viscosity. In the presence of HClO, the HClO-responsive moiety within LNX-HClO undergoes self-immolative cleavage to generate LNX-OH, which can facilitate intramolecular charge transfer (ICT) process. Subsequently, the high viscosity restricts bond rotation in LNX-OH, thereby suppressing the twisted intramolecular charge transfer (TICT) pathway. As a result, a significant fluorescence enhancement at 700 nm with a large Stokes shift of 150 nm is observed. Furthermore, in vitro experiments and cellular fluorescence imaging demonstrate that the probe possesses high selectivity, sensitivity, and excellent lysosome-targeting ability. Crucially, LNX-HClO has enabled the accurate diagnosis of AKI (drug-induced/ischemia-reperfusion injury-induced AKI) and the assessment of therapeutic efficacy.
Significance:
This probe (LNX-HClO) has been successfully utilized for imaging HClO and viscosity in vitro and in vivo. It leverages specific small biological molecules and biophysical parameters to offer the potential to substantially minimize false positive signals, thereby improving diagnostic accuracy. It was expected to provide a valuable tool for AKI-related research and clinical applications.
