Hu Yan, Zhang Hongshuai, Ding Yiteng, Chen Weirui, Pan Changqie, He Longwei, Cheng Dan, Yuan Lin
Department of Gastroenterology, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China Hengyang 421002 Hunan China
Department of Thoracic Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University Changsha 410013 China
Chem Sci. 2025 Apr 24. doi: 10.1039/d5sc01488c.
Diabetes and its complications have drawn growing research attention due to their detrimental effects on human health. Although optical probes have been used to help understand many aspects of diabetes, the lung diseases caused by diabetes remain unclear and have rarely been explored. Herein, a tandem-reaction (TR) strategy is proposed based on the adjacent diol esterification-crosslinking reaction and the nicotinamide reduction reaction of nicotinamide adenine dinucleotide (NADH) to design a lung-targeting near-infrared (NIR) small molecule probe (NBON) for accurate imaging of diabetic lung diseases. NBON was designed by coupling a phenylboronic acid analog that can form borate ester bonds by reversibly binding with NADH an esterification-crosslinking reaction. Streptozotocin (STZ)-induced diabetic mice and metformin (MET)/epalrestat (EPS)-repaired model studies demonstrated that NBON allowed the sensitive imaging of NADH for lung disease diagnosis and therapeutic monitoring. The proposed antioxidant mechanism by which EPS alleviates diabetic lung disease was studied for the first time in living cells and . Furthermore, NBON was successfully applied in the detection of NADH in tumors and lung metastases. Overall, this work provides a general platform for a NIR NADH probe design, and advances the development of NADH probes for mechanistic studies in lung diseases.
糖尿病及其并发症因其对人类健康的有害影响而受到越来越多的研究关注。尽管光学探针已被用于帮助了解糖尿病的许多方面，但糖尿病引发的肺部疾病仍不清楚，且很少有人探索。在此，基于邻二醇酯化交联反应和烟酰胺腺嘌呤二核苷酸（NADH）的烟酰胺还原反应，提出了一种串联反应（TR）策略，以设计一种用于糖尿病肺部疾病精确成像的肺靶向近红外（NIR）小分子探针（NBON）。NBON是通过将一种能与NADH可逆结合形成硼酸酯键的苯硼酸类似物与酯化交联反应偶联而设计的。链脲佐菌素（STZ）诱导的糖尿病小鼠和二甲双胍（MET）/依帕司他（EPS）修复模型研究表明，NBON能够对NADH进行灵敏成像，用于肺部疾病的诊断和治疗监测。首次在活细胞中研究了EPS减轻糖尿病肺部疾病的抗氧化机制。此外，NBON成功应用于肿瘤和肺转移灶中NADH的检测。总体而言，这项工作为近红外NADH探针设计提供了一个通用平台，并推动了用于肺部疾病机制研究的NADH探针的发展。
