Mitochondria-Targeted Ratiometric Chemdosimeter to Detect Hypochlorite Acid for Monitoring the Drug-Damaged Liver and Kidney

Abstract

Liver and kidney injury caused by drug toxicity is a serious threat to human health. Acetaminophenol (APAP), as a common antipyretic and analgesic drug, inevitably causes injury. When it is overused, hypochlorous acid (HClO) is excessively generated due to metabolic abnormalities, resulting in the accumulation of HClO in the mitochondria of liver and kidney tissues and causing damage. In this study, we designed a series of HClO responsive ratiometric chemdosimeter NRH-X (NRH-O, NRH-S, and NRH-C) to evaluate liver and kidney injury, and found that NRH-O has a specific sensitive response to HClO. NRH-O can not only monitor the variations of endogenous HClO content of living cells by fluorescence ratio changes in the mitochondria but also detect the upregulation of HClO induced by APAP. In addition, NRH-O can also be used for anatomic diagnosis of liver and kidney injury by fluorescence ratio imaging of HClO in the tissues of inflammatory mice.

A ratiometric nanoprobe for the in vivo bioimaging of hypochlorous acid to detect drug-damaged liver and kidneys

“…The nanoprobe was produced by an improved design idea from the literature (Scheme S1, ESI †). [59][60][61] As reported in previous work, the absorption and emission wavelengths of the probe NRH-680 were 680 nm and 730 nm, respectively, which was not responsive to HClO. In order to improve the sensitivity of the probe molecules to HClO, the structure of NRH-680 was modified to lengthen the molecular conjugate structure by adding a double bond to obtain the new probe NRH-800.…”

Vision for Ratiometric Nanoprobes: In Vivo Noninvasive Visualization and Readout of Physiological Hallmarks

“…, 1000–1700 nm) region transmitted within human tissues encounter minimized scattering and absorption . Therefore, although developing NIR-I emissive optical- and photoacoustic-based RNPs is still actively ongoing, ,,− constructing NIR-II sensors is more favorable for high-performance in vivo imaging from deep-seated organs.…”

Mitochondrial-Targeted Ratiometric Near-Infrared Fluorescence Probe for Monitoring Nitric Oxide in Rheumatoid Arthritis

“…Molecular fluorescent probes have attracted much attention due to their high sensitivity and high selectivity, enabling accurate identification of target analytes and noninvasive real-time observation in vivo . − Reactive oxygen species (ROS) and reactive nitrogen species (RNS) levels increase during the progression of RA disease. − Several fluorescent probes for the detection of reactive oxygen and nitrogen species have been reported for the diagnosis and monitoring of arthritis. ,− In physiological disorders, activated macrophages produce high levels of nitric oxide (NO), which can upregulate osteoclasts, destroy cartilage, and recruit other immune cells to cause inflammation, and thus NO is often thought to be involved in joint damage. − Therefore, the detection of NO is of great significance for the early diagnosis of RA. , The reported NO probes are mainly composed of o -phenylenediamine and aromatic secondary amines, which specifically react with NO to produce fluorescent signals. − Among them, probes with o -phenylenediamine structure are typically based on photoinduced electron transfer (PET) that undergo enhanced fluorescence in the presence of NO. − Compared with to the single-channel imaging mode of the “turn-on” type probes, the ratio-metric fluorescent probes based on the intramolecular charge transfer (ICT) effect are preferred for NO imaging with high-resolution and self-calibration, which can be quantitatively detected by the ratio and effectively reduce the background signal interference to realize accurate spatial-temporal detection of NO. − However, ICT-based small molecule NIR fluorescent probes with o -phenylenediamine have not been reported.…”