Protein/Gold Nanoparticle-Based Sensors for Monitoring the Progression of Adriamycin Nephropathy

Adriamycin (ADR) nephropathy is a typical proteinuric renal disease, whose underlying mechanism is complicated but closely relevant to podocyte injury, leading to persistent proteinuria. Moreover, proteinuria is not only a unique clinic pathological manifestation of many kidney diseases but also an independent predictor of the diagnosis of nephropathy. Hence, monitoring the process of ADR nephropathy based on the variation of urinary proteins will be conducive to understand the pathogenesis of proteinuric nephropathy. In this work, the protein/gold nanoparticle-based sensors have been constructed through electrostatic interaction of amino headgroup-terminated gold nanoparticles (Ami-AuNPs) with three fluorophore-modified proteins (FMPs) to monitor and evaluate the process of ADR nephropathy by detecting and identifying subtle variation of urinary proteins. In the presence of urinary proteins with varied charges at different damage stages in ADR nephropathy, the binding equilibrium between Ami-AuNPs and FMPs will be broken due to competitive binding, thereby modulating the fluorescence response. Also, the protein/gold nanoparticle-based sensors are also able to classify the progression of ADR nephropathy into seven stages and evaluate the protective effect of Huangkui capsule using principal component analysis and linear discriminant analysis. Additionally, the reliability of the sensing method is further verified by the morphological changes of podocytes and significant differences in the expression of nephrin and podocin. Notably, this sensing strategy promises to be a powerful technique for monitoring the progress of ADR nephropathy and evaluating the corresponding protective drugs for expediting research in clinical diagnosis and treatment of proteinuric nephropathy.