SERS-Based Ultralow Concentration Detection of Anticancer Gemcitabine Using Size-Controlled Silver Nanoparticles

Quantitative detection of trace concentrations of anticancer drug gemcitabine (GMC) was successfully established using the surface-enhanced Raman scattering (SERS) analytical approach. Chemically reduced size-controlled silver nanoparticles (AgNPs) were used as an active SERS substrate which exhibited a significant electrostatic interaction with the target molecules. The developed analytical approach depicted a viable and sensitive means leading to a low limit of detection of 1.5 × 10^–10 M and a limit of quantification 3.5 × 10^–10 M in aqueous media with an excellent recovery (98%). A consistent linear response featuring a wide dynamic range (10^–4–10^–9 M) with a coefficient of regression (R²) of 0.9987 could be also achieved. The enhancement in the Raman signal intensities associated with wavenumber shifts was carefully analyzed, and the corresponding vibrational modes were assigned. Density functional theory assessments of the possible drug-substrate interaction scenarios were carried out, and four potential modes of interaction through the primary amine group, the hydroxyl groups, and the pyrimidine nitrogen were proposed.