College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences, Shandong Normal University, Jinan 250014, People's Republic of China.
Department of Chemistry, University of Bath, Bath BA2 7AY, U.K.
J Am Chem Soc. 2022 Aug 3;144(30):13586-13599. doi: 10.1021/jacs.2c03832. Epub 2022 Jul 6.
Hepatic ischemia-reperfusion injury (HIRI) is responsible for postoperative liver dysfunction and liver failure. Precise and rapid navigation of HIRI lesions is critical for early warning and timely development of pretreatment plans. Available methods for assaying liver injury fail to provide the exact location of lesions in real time intraoperatively. HIRI is intimately associated with oxidative stress which impairs lysosomal degradative function, leading to significant changes in lysosomal viscosity. Therefore, lysosomal viscosity is a potential biomarker for the precise targeting of HIRI. Hence, we developed a viscosity-activatable second near-infrared window fluorescent probe (NP-V) for the detection of lysosomal viscosity in hepatocytes and mice during HIRI. A reactive oxygen species-malondialdehyde-cathepsin B signaling pathway during HIRI was established. We further conducted high signal-to-background ratio NIR-II fluorescence imaging of HIRI mice. The contour and boundary of liver lesions were delineated, and as such the precise intraoperative resection of the lesion area was implemented. This research demonstrates the potential of NP-V as a dual-functional probe for the elucidation of HIRI pathogenesis and the direct navigation of HIRI lesions in clinical applications.
肝缺血再灌注损伤（HIRI）是导致术后肝功能障碍和肝功能衰竭的原因。精确和快速地定位 HIRI 损伤对于早期预警和及时制定预处理计划至关重要。现有的肝功能损伤检测方法无法在术中实时提供病变的确切位置。HIRI 与氧化应激密切相关，氧化应激会损害溶酶体的降解功能，导致溶酶体粘度发生显著变化。因此，溶酶体粘度是 HIRI 精确靶向的潜在生物标志物。因此，我们开发了一种粘度激活型近红外二区荧光探针（NP-V），用于在 HIRI 期间检测肝细胞和小鼠中的溶酶体粘度。建立了 HIRI 过程中的活性氧-丙二醛-组织蛋白酶 B 信号通路。我们进一步对 HIRI 小鼠进行了高信噪比的近红外二区荧光成像。描绘了肝损伤的轮廓和边界，从而实现了病变区域的精确术中切除。这项研究表明，NP-V 作为一种双功能探针，具有阐明 HIRI 发病机制和直接导航临床应用中 HIRI 病变的潜力。
