State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China; Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Key Laboratory of Auxiliary Chemistry and Technology for Chemical Industry, Ministry of Education, Shaanxi University of Science and Technology, Xi'an, 710021, China; Shaanxi Collaborative Innovation Center of Industrial Auxiliary Chemistry & Technology, Shaanxi University of Science & Technology, Xi'an, 710021, China.
Biosens Bioelectron. 2024 Aug 15;258:116344. doi: 10.1016/j.bios.2024.116344. Epub 2024 Apr 27.
Autophagy is an essential degradative process that governs the renewal of organelle and maintains the homeostasis of cellular microenvironment. Its dysregulation has been demonstrated to be an indicator for neuroinflammation. To elucidate the interrelationship between neuroinflammation and autophagy, optical probes are ideal tools as they offer a number of advantages such as high spatiotemporal resolution and non-invasive sensing, which help to visualize the physiological and pathological functions of interested analytes. However, single autophagy parameter-response probes may generate false-positive results since they cannot distinguish between neuroinflammation and other autophagic stimuli. In contrast, chemosensors that respond to two (or more) targets can improve selectivity by qualifying response conditions. Herein, a "dual-key-and-lock" strategy was applied to construct probe (Vis-NO) to selectively recognize autophagy under inflammation out of other stimuli. The red fluorescence of Vis-NO was lit up only in the simultaneously presence of high viscosity and nitric oxide (NO) in lysosome. Due to the characteristics of high viscosity and overexpressed NO within lysosomes, Vis-NO could be used to selectively identify autophagy during neuroinflammation, providing expanding insights into the interrelationship between autophagy, neuroinflammation and stroke in pathology, and informing about the mechanisms through which autophagy regulates inflammation.
自噬是一种重要的降解过程，它控制着细胞器的更新，并维持细胞微环境的稳态。其失调已被证明是神经炎症的一个指标。为了阐明神经炎症和自噬之间的相互关系，光学探针是理想的工具，因为它们具有许多优点，如高时空分辨率和非侵入性传感，这有助于可视化感兴趣分析物的生理和病理功能。然而，由于单一代谢参数反应探针不能区分神经炎症和其他自噬刺激，因此可能会产生假阳性结果。相比之下，能够响应两个（或更多）目标的化学传感器可以通过限定响应条件来提高选择性。在这里，采用了“双钥匙和锁”策略来构建探针（Vis-NO），以便在其他刺激物存在的情况下，选择性地识别炎症下的自噬。只有在溶酶体中同时存在高粘度和一氧化氮（NO）的情况下，Vis-NO 的红色荧光才会被点亮。由于溶酶体中存在高粘度和过表达的 NO 的特点，Vis-NO 可用于在神经炎症期间选择性地识别自噬，从而深入了解自噬、神经炎症和中风在病理学中的相互关系，并了解自噬调节炎症的机制。
