High-throughput methotrexate sensing strategy based on a chemometrically assisted pH-switchable optical nanosensor

Abstract

In the present work, a methotrexate (MTX) optical nanosensor involving the generation of a double pH gradient in which silver nanoclusters (AgNCs) act as an optical probe is presented. The proposed strategy is based on the pH-dependent agglomeration and dispersion behavior of the AgNCs and the consequent reversible changes in the spectroscopic signal. MTX is an antineoplastic drug used in high doses (HD) for the treatment of different types of cancer. Interestingly, the presence of the AgNCs enhances the signal of MTX, a phenomenon that was exploited to generate a simple, fast, and sensitive method for MTX quantitation in the presence of uncalibrated components based on second-order data generation and chemometric data modeling. The successful calibration models were obtained by unfolded partial least squares coupled to residual bilinearization, which was able to deal with data with high spectral collinearity while achieving the second-order advantage. The proposed sensing strategy reached limits of detection and quantitation of 3.3 nmol L–1 and 10.1 nmol L–1, respectively. These results support the applicability of the method for the detection and quantitation of MTX at clinically relevant concentrations, considering that plasma levels after the HD-MTX treatment should reach concentrations of 0.1 µmol L–1 at 72 h to minimize side effects. Furthermore, the generation of second-order data and chemometric data modeling allowed the accurate prediction of MTX in the presence of uncalibrated compounds. The developed sensing platform is presented as an alternative of great interest, which allows the simple, fast, sensitive, and selective quantitation of MTX.