State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China; Shenzhen Institute for Drug Control, Shenzhen, 518057, China.
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
Anal Chim Acta. 2021 May 22;1160:338447. doi: 10.1016/j.aca.2021.338447. Epub 2021 Mar 25.
Drug-induced kidney injury causes structural or functional abnormalities of kidney, seriously affecting clinical practice and drug discovery. However, rapid and effective identification of nephrotoxic drug mechanisms is yet a challenging task arising from the complexity and diversity of various nephrotoxic mechanisms. Herein, we have constructed a polydopamine-polyethyleneimine/quantum dots sensor to instantaneously read out the nephrotoxic drugs mechanisms based on the disparate cell surface phenotypes. Cell surface components induced by multiple nephrotoxic drugs can change the fluorescence emission of multicolor quantum dots, generating their corresponding fluorescent fingerprints. The fluorescence response signatures induced by different nephrotoxic agents are gained with 84% accuracy via linear discriminant analysis. Furthermore, taking the time-toxicity relationship into consideration, dynamic fluorescent fingerprint is obtained through continuous monitoring the progress of renal cell damage, achieving 100% precise classification for nephrotoxic mechanisms of four types of antibiotics. Notably, the fluorescent fingerprint-based high-throughput sensor has been demonstrated by successfully distinguishing nephrotoxic drugs in seconds, employing a promising protocol to discriminate the specific mechanism of nephrotoxic drugs, as well as drug safety evaluation.
药物性肾损伤导致肾脏结构或功能异常，严重影响临床实践和药物发现。然而，由于各种肾毒性机制的复杂性和多样性，快速有效地识别肾毒性药物的机制仍然是一项具有挑战性的任务。在此，我们构建了一种聚多巴胺-聚乙烯亚胺/量子点传感器，可基于不同的细胞表面表型即时读取肾毒性药物的机制。多种肾毒性药物诱导的细胞表面成分会改变多色量子点的荧光发射，产生相应的荧光指纹。通过线性判别分析，可将不同肾毒性药物诱导的荧光响应特征以 84%的准确率获得。此外，考虑到时间-毒性关系，通过连续监测肾细胞损伤的进展，可以获得动态荧光指纹，对四种类型抗生素的肾毒性机制进行 100%精确分类。值得注意的是，基于荧光指纹的高通量传感器已成功用于在数秒内区分肾毒性药物，为区分肾毒性药物的特定机制以及药物安全性评估提供了一种很有前途的方案。
