Ultrasensitive SERS Substrate for Label-Free Therapeutic-Drug Monitoring of Paclitaxel and Cyclophosphamide in Blood Serum

Abstract

Surface-enhanced Raman spectroscopy (SERS) has recently emerged as an innovative tool for therapeutic-drug monitoring (TDM), making it an ideal candidate for personalized treatment. Herein, we report a layer-by-layer (LbL) approach for the fabrication of a highly reproducible hybrid SERS substrate based on graphene oxide (GO)-supported l-cysteine-functionalized starlike gold nanoparticles (SAuNPs). These designed substrates were utilized for TDM of paclitaxel and cyclophosphamide in blood serum. The SAuNPs’ efficient binding at the edges of GO creates a better SERS hotspot with enhanced Raman sensitivity because of the spacing of ∼2.28 nm between the SAuNPs. In addition, the hierarchically modified substrate with a self-assembled monolayer of zwitterionic amino acid l-cysteines acts like a brush layer to prevent SERS-hotspot blockages and fouling by blood-serum proteins. The antifouling nature of the substrate was determined quantitatively by a bichinchonic acid assay using bovine-serum albumin (BSA) as a protein model on the l-cysteine SAuNPs@GO hybrid substrate (the test) and a cysteamine SAuNPs@GO substrate (the control). The l-cysteine SAuNPs@GO hybrid exhibited 80.57% lower BSA fouling compared with that of the cysteamine SAuNPs@GO substrate. The SERS spectra were acquired within 20 s, with detection limits of 1.5 × 10–8 M for paclitaxel and 5 × 10–9 M for cyclophosphamide in blood serum. Such sensitivities are 4 times and 1 order of magnitude higher than the currently available sophisticated analytical techniques, which involve high costs with each analysis.

Detection of aspirin traces in blood by means of surface‐enhanced Raman scattering spectroscopy

“…The SERS method is also versatile and allows various technical approaches for the enhancement of the Raman scattering signal . Thus, SERS is being proposed as a cheaper alternative for detection and monitoring of various drugs . Previously, the SERS method employing microgels containing agglomerates of silver nanocubes was used for the detection of aspirin in the blood .…”

Algunas aplicaciones de la nanofotónica en la biomedicina

“…La MP toma en cuenta que cada organismo reacciona y/o asimila un medicamento en forma diferente, por lo cual, conocer con mayor precisión la cantidad exacta de medicamento que asimila cada cuerpo ayuda a mejora la terapia y reducir los problemas toxicológicos. Un análisis detallado de la preparación de NPs de oro tipo estrella, su funcionalización, activación del grafeno, así como resultados en la detección de medicamentos se reporta en Panikar et al (2019).…”

Potential of Raman spectroscopy for the analysis of plasma/serum in the liquid state: recent advances

“…Vibrational spectroscopic techniques, both Raman and Infrared (IR) absorption, have been extensively explored over the last two decades for obtaining the biochemical composition of bodily fluids in the field of biomedical analysis [1][2][3][4][5][6][7][8][9][10]. The sensitivity to detect subtle changes in the biochemical composition and ability to detect the presence of specific biomarkers or drugs makes vibrational spectroscopy an ideal tool for the early diagnosis of various pathologies [11][12][13][14] and therapeutic drug monitoring [15][16][17]. Both techniques are truly label free, rapid, cost-effective, easy to operate, non-destructive and provide the unique molecular fingerprint of the sample with minimal sample preparation steps.…”