Affiliation:
1. Shanghai Key Laboratory of Functional Materials Chemistry Key Laboratory for Advanced Materials and Institute of Fine Chemicals Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Feringa Nobel Prize Scientist Joint Research Center Frontiers Science Center for Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science and Technology Shanghai China
2. Department of Pathology Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
3. Research Center for Marine Drugs Department of Pharmacy Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai China
4. Department of Laboratory Medicine Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
Abstract
AbstractUrinary microalbumin (mALB) serves as an exceptionally sensitive indicator for the early detection of kidney damage, playing a pivotal role in identifying chronic renal failure and kidney lesions in individuals. Nevertheless, the current fluorescent methodologies for point‐of‐care (POC) diagnosis of mALB in real urine still exhibit suboptimal performance. Herein, the development and synthesis of QM‐N2, an albumin‐activated near‐infrared (NIR) aggregation‐induced emission (AIE) fluorescent probe, are presented. The strategic incorporation and positioning of quaternary ammonium salts within the quinoline‐malononitrile (QM) scaffold significantly influence solubility and luminescence characteristics. Specifically, the quaternary ammonium salt‐free variant, QM‐OH, and the quaternary ammonium salt integrated at the donor function group (DFG) site, QM‐N1, display limited solubility in aqueous solutions while demonstrating a distinct fluorescence signal. Conversely, the incorporation of quaternary ammonium salt at the conformational functional group (CFG) site in QM‐N2 imparts superior dispersibility in water and reduces the initial fluorescence. Furthermore, the integration of a well‐defined D‐π‐A structure within QM‐N2 enables itself with near‐infrared emission, which is crucial for mitigating interference from autofluorescence present in urine samples. Upon interaction with albumin, QM‐N2 forms a tight bond with the IIA site of the subdomain of human serum albumin (HSA), inducing alterations in protein configuration and constraining the intrinsic motion of fluorescent molecules. This interaction induces fluorescence, facilitating the sensitive detection of trace albumin. Ultimately, QM‐N2 is applied for POC testing of mALB using portable equipment, particularly in the diagnosis of mALB‐related diseases, notably chronic renal failure. This positioning underscores its potential as an ideal candidate for self‐health measurement at home or in community hospitals.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
China Postdoctoral Science Foundation