A novel ESIPT fluorescent probe for early detection and assessment of ferroptosis-mediated acute kidney injury via peroxynitrite fluctuation

• Published in: Analytica chimica acta Vol. 1308; p. 342611
• Main Authors: Chen, Miao, Lin, Shuiling, Tang, Bingbing, Tian, Tian, Leng, Yahui, Liu, Danwen, Wang, Kelong, Geng, Yi, Luo, Zhiguo, Shen, Li, Chen, Tongsheng
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.06.2024
• Subjects: Acute kidney injury; Acute Kidney Injury - chemically induced; Animals; Early Diagnosis; Ferroptosis; Ferroptosis - drug effects; Fluorescence probe; Fluorescent Dyes - chemical synthesis; Fluorescent Dyes - chemistry; Humans; Mice; Molecular Structure; Optical Imaging; Peroxynitrite; Peroxynitrous Acid - metabolism; Zebrafish; Ferroptosis; Peroxynitrite; Fluorescence probe; Acute kidney injury
• ISSN: 0003-2670; 1873-4324
• DOI: 10.1016/j.aca.2024.342611

Acute kidney injury (AKI) poses a severe risk to public health, mostly manifested by damage and death of renal tubular epithelial cells. However, routine blood examination, a conventional approach for clinical detection of AKI, is not available for identifying early-stage AKI. Plenty of reported methods were lack of early biomarkers and real time evaluation tools, which resulted in a vital challenge for early diagnosis of AKI. Therefore, developing novel probes for early detection and assessment of AKI is exceedingly crucial. Based on ESIPT mechanism, a new fluorescent probe (MEO-NO) with 2-(2′-hydroxyphenyl) benzothiazole (HBT) derivatives as fluorophore has been synthesized for dynamic imaging peroxynitrite (ONOO−) levels in ferroptosis-mediated AKI. Upon the addition of ONOO−, MEO-NO exhibited obvious fluorescence changes, a significant Stokes shift (130 nm) and rapid response (approximately 45 s), and featured exceptional sensitivity (LOD = 7.28 nM) as well as high selectivity from the competitive species at physiological pH. In addition, MEO-NO was conducive to the biological depth imaging ONOO− in cells, zebrafish, and mice. Importantly, MEO-NO could monitor ONOO− levels during sorafenib-induced ferroptosis and CP-induced AKI. With the assistance of MEO-NO, we successfully visualized and tracked ONOO− variations for early detection and assessment of ferroptosis-mediated AKI in cells, zebrafish and mice models. Benefiting from the superior performance of MEO-NO, experimental results further demonstrated that the levels of ONOO− was overexpressed during ferroptosis-mediated AKI in cells, zebrafish, and mice models. The developed novel probe MEO-NO provided a strong visualization tool for imagining ONOO−, which might be a potential method for the prevention, diagnosis, and treatment of ferroptosis-mediated AKI. In this work, a novel ESIPT turn-on fluorescent probe (MEO-NO) for sensing ONOO− with a large Stokes shift (130 nm) had been designed and synthesized. MEO-NO had a rapid response time (around 45 s) and ultra-sensitivity (7.28 nM) for monitoring ONOO− in an aqueous buffer. MEO-NO revealed a close relevance between ONOO− and ferroptotic progression. Meanwhile, we could also utilize MEO-NO to monitor the fluctuation of ONOO− in ferroptosis-mediated acute kidney injury. We anticipate that the novel fluorescence detection tool can enlighten this subject and assist in early diagnosis and accurate therapy of acute kidney injury. [Display omitted] •A new ESIPT fluorescent probe MEO-NO was prepared for imaging ONOO− fluctuations in ferroptosis-mediated AKI.•MEO-NO exhibited a large Stokes shift (130 nm), rapid response (around 45 s), and high selectivity towards ONOO−.•MEO-NO was good for the biological depth imaging ONOO− in cells, zebrafish, and mice.•MEO-NO monitored ONOO− during sorafenib-induced ferroptosis and early detection and assessment of ferroptosis-mediated AKI.