A nanosensor for precise discrimination of nephrotoxic drug mechanisms via dynamic fluorescence fingerprint strategy

Abstract

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.