Selective fluorescence turn-on detection of combination cisplatin-etoposide chemotherapy based on N-CDs/GSH-CuNCs nanoprobe

Abstract

Cisplatin (CIS) and etoposide (ETP) combination therapy is highly effective for treating various cancers. However, the potential for pharmacokinetic interactions between these drugs necessitates selective sensing methods to quantitate both CIS and ETP levels in patient's plasma. This work develops a dual fluorescence probe strategy using glutathione-capped copper nanoclusters (GSH-CuNCs) and nitrogen-doped carbon dots (N-CDs) for the simultaneous analysis of CIS and ETP. The fluorescence signal of GSH-CuNCs at 615 nm increased linearly with CIS concentration while the N-CD emission at 480 nm remained unaffected. Conversely, the N-CD fluorescence was selectively enhanced by ETP with no interference with the CuNC fluorescence. Extensive materials characterization including UV-vis, fluorescence spectroscopy, XRD, and TEM confirmed the synthesis of the nanoprobes. The sensor showed high sensitivity with limits of detection of 6.95 ng mL^-1 for CIS and 7.63 ng mL^-1 for ETP along with excellent selectivity against potential interferences in rabbit plasma. Method feasibility was demonstrated with application to real rabbit plasma samples. The method was further applied to estimate the pharmacokinetic parameters of CIS before and after ETP coadministration. The dual nanoprobe sensing strategy enables rapid and selective quantitation of CIS and ETP levels to facilitate therapeutic drug monitoring and optimization of combination chemotherapy regimens.

Fig. 1. (A) TEM image of N-CDs, (B) TEM image of CuNCs, (C) FT-IR of N-CDs and GSH-CuNCs, (D) high resolution XPS spectra of the Cu 2p in CuNCs (E) XRD pattern of N-CDs.

Fig. 2. (A) UV-visible absorption (black), fluorescence excitation (red), and emission (blue) spectra of the N-CDs. Inset displays photographs under ambient light and 365 nm UV illumination. (B) Emission spectra of the N-CDs at excitation wavelengths from 320 to 410 nm. (C) UV-vis absorption (black), excitation (red) and emission (blue) spectra for the glutathione-capped copper nanoclusters. Inset shows images under visible and UV light. (D) Fluorescence emission spectra of the Cu nanoclusters obtained with excitation wavelengths ranging from 350 to 410 nm.

Fig. 3. (A) The influence of variation of concentrations of CIS (20–160 ng mL⁻¹) and ETP (25–200 ng mL⁻¹) on the emission intensity of N-CDs/GSH-CuNCs. (B) Relationship of (F/F₀) against concentration of CIS/ETP.

Fig. 4. (A) The selectivity GSH-CuNCs towards CIS in the presence of different interferents species. (B) The selectivity of N-CDs towards ETP in the existence of different interferents.

Fig. 5. Comparison between mean CIS concentrations over time with and without ETP administration.