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A Rapid and Quantitative Fluorimetric Method for Protein-Targeting Small Molecule Drug Screening
Published on: October 16, 2015
The screening of drug-induced nephrotoxicity using gold nanocluster-based ratiometric fluorescent probes
1State Key Laboratory of Natural Medicine, the School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China. pjj@cpu.edu.cn.
Abstract:
Herbal medicines are potential candidates for the treatment of various diseases, but their medication safety remains poorly regulated. Current screening methods for the herbal medicine-induced nephrotoxic effects include histological and serological assessments, which often fail to reflect the kidney dysfunction instantly. Here we report a ratiometric fluorescence approach for the rapid and facile screening of drug-induced acute kidney injury using chromophore-modified gold nanoclusters. These gold nanoclusters are highly sensitive to reactive oxygen species (ROS), with a detection limit of 14 nM for ˙OH. After passing through the glomerular filtration barrier, the gold nanocluster-based probes can quantify the fluctuation of the ROS level in the kidneys and evaluate the risk of drug-induced nephrotoxicity. We further employed nephrotoxic triptolide as the model drug and the screening of drug-induced early renal injury was demonstrated using the nanoprobes, which is unattainable by conventional diagnostic approaches. Our fluorescent probes also allow the identification of other nephrotoxic components from herbal medicine such as aristolochine, providing a high-throughput strategy for the screening of herbal supplement-induced nephrotoxicity.

