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用于肾功能障碍的近红外二区荧光成像的可经肾清除的分子半导体

Renal-clearable Molecular Semiconductor for Second Near-Infrared Fluorescence Imaging of Kidney Dysfunction.

机构信息

School of Chemical and Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457, Singapore.

Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing, 210023, China.

出版信息

Angew Chem Int Ed Engl. 2019 Oct 14;58(42):15120-15127. doi: 10.1002/anie.201909560. Epub 2019 Sep 5.

Abstract

Real-time imaging of kidney function is important to assess the nephrotoxicity of drugs and monitor the progression of renal diseases; however, it remains challenging because of the lack of optical agents with high renal clearance and high signal-to-background ratio (SBR). Herein, a second near-infrared (NIR-II) fluorescent molecular semiconductor (CDIR2) is synthesized for real-time imaging of kidney dysfunction in living mice. CDIR2 not only has a high renal clearance efficiency (≈90 % injection dosage at 24 h post-injection), but also solely undergoes glomerular filtration into urine without being reabsorbed and secreted in renal tubules. Such a unidirectional renal clearance pathway of CDIR2 permits real-time monitoring of kidney dysfunction in living mice upon nephrotoxic exposure. Thus, this study not only introduces a molecular renal probe but also provides useful molecular guidelines to increase the renal clearance efficiency of NIR-II fluorescent agents.

摘要

实时成像肾脏功能对于评估药物的肾毒性和监测肾脏疾病的进展非常重要;然而,由于缺乏具有高肾清除率和高信噪比(SBR)的光学试剂,这仍然具有挑战性。在此,合成了一种第二代近红外(NIR-II)荧光分子半导体(CDIR2),用于活体小鼠肾功能的实时成像。CDIR2 不仅具有高肾清除效率(≈注射后 24 小时 90%的注射剂量),而且仅通过肾小球滤过进入尿液,而不在肾小管中被重吸收和分泌。CDIR2 的这种单向肾清除途径允许在肾毒性暴露时实时监测活体小鼠的肾功能障碍。因此,本研究不仅介绍了一种分子肾探针,而且为提高 NIR-II 荧光试剂的肾清除效率提供了有用的分子指导原则。

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