Lv Zhangkang, Wang Jing, Xu Jinyuan, Chen Xiaoshan, Lu Dongxue, Huang Jingting, Shen Xing-Can, Chen Hua
Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Guangxi Key Laboratory of Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004, P. R. China.
Adv Healthc Mater. 2025 May;14(12):e2500273. doi: 10.1002/adhm.202500273. Epub 2025 Mar 24.
High-fidelity kidney function imaging is important for assessing the nephrotoxicity of drugs and diagnosing renal diseases. However, the current challenges in achieving accurate kidney imaging include unspecific signal enhancement due to albumin binding and relatively low distribution of imaging agents in kidneys. Here, for the first time, a side-chain engineering strategy that incorporates hydrophilic six-membered heterocycles into aza-hemicyanine for generating high-performance kidney imaging agents with protein-interference-free and kidney-targeting features is proposed. Based on these unique aza-hemicyanine dyes, the first kidney-targeting and albumin-insensitive HS near-infrared (NIR) fluorescent probe NA-HS is designed, which demonstrates effective kidney distribution following intravenous injection and is specifically activated by HS. The designed probe presents a highly rapid, selective and sensitive response to HS with a detection limit as low as 24.21 nm. Additionally, it successfully achieves real-time in vivo NIR fluorescence imaging of HS during erastin/cisplatin induced renal ferroptosis. Moreover, it also enables rapid detection of HS through in vitro optical urinalysis, offering significant diagnostic value for renal ferroptosis. Overall, this study not only presents a practical kidney-targeting HS fluorescent probe NA-HS with increased imaging accuracy but also provides promising kidney-targeting and albumin-insensitive aza-hemicyanine dyes for further development of kidney disease-related probes.
高保真肾功能成像对于评估药物的肾毒性和诊断肾脏疾病至关重要。然而，目前实现准确肾脏成像面临的挑战包括由于白蛋白结合导致的非特异性信号增强以及成像剂在肾脏中的相对低分布。在此，首次提出了一种侧链工程策略，即将亲水性六元杂环引入氮杂半菁中，以生成具有无蛋白质干扰和肾脏靶向特征的高性能肾脏成像剂。基于这些独特的氮杂半菁染料，设计了首个肾脏靶向且对白蛋白不敏感的HS近红外（NIR）荧光探针NA-HS，该探针在静脉注射后显示出有效的肾脏分布，并被HS特异性激活。所设计的探针呈现出对HS高度快速、选择性和灵敏的响应，检测限低至24.21nm。此外，它在erastin/顺铂诱导的肾铁死亡过程中成功实现了HS的体内实时近红外荧光成像。而且，它还能够通过体外光学尿液分析快速检测HS，为肾铁死亡提供了重要的诊断价值。总体而言，本研究不仅展示了一种具有更高成像准确性的实用肾脏靶向HS荧光探针NA-HS，还为进一步开发与肾脏疾病相关的探针提供了有前景的肾脏靶向且对白蛋白不敏感的氮杂半菁染料。
