Core/shell upconversion nanoparticles with intense fluorescence for detecting doxorubicin in vivo

Abstract

Doxorubicin (Dox) is a chemotherapy medication used to treat cancer. Herein, we report a rapid and efficient method for detecting Dox in vivo based on a NaGdF₄:Yb³⁺,Er³⁺@NaYF₄ core/shell upconversion nanoparticles (UCNPs) probe. We found that the intensity ratio of green to red emission (IGVRE) bands of the core/shell NaGdF₄:Yb³⁺,Er³⁺@NaYF₄ nanoparticles was sensitive to Dox in blood samples, and drops as the concentration of Dox increases. In addition, the proposed UCNPs probe possessed the advantage that no nanoparticles leaked into the living body, thus overcoming the intrinsic defect (difficulty in removing UCNPs from blood vessels) of the fluorescence resonance energy transfer (FRET) approach. This proposed UCNP probe design and results may provide some guidance for the real-time and efficient detection of Dox, and can be helpful in biomedical applications.

Fig. 1. (a and b) TEM images of NaGdF₄:18% Yb³⁺,2%Er³⁺@NaYF₄ core/shell nanoparticles. (c) The corresponding high-resolution TEM images.

Fig. 2. Energy dispersive spectrum (EDS) of NaGdF₄:Yb³⁺,Er³⁺@NaYF₄ core/shell nanoparticles.

Fig. 3. XRD spectrum of NaGdF₄:18% Yb³⁺,2%Er³⁺@NaYF₄ core/shell particles.

Fig. 4. Room temperature upconversion emission spectrum of core/shell NaGdF₄:18% Yb³⁺,2%Er³⁺@NaYF₄ and bare NaGdF₄:18% Yb³⁺,2%Er³⁺ nanoparticles. The inset: the photograph of core/shell UCNPs dispersed in CGT under the 0.08 W cm⁻² laser power at 980 nm excitation.

Fig. 5. (a) Room-temperature upconversion fluorescence spectra of NaGdF₄:18% Yb³⁺,2%Er³⁺@NaYF₄ core/shell particles with different concentrations of doxorubicin (0 μg mL⁻¹, 20 μg mL⁻¹, 50 μg mL⁻¹, 70 μg mL⁻¹, and 100 μg mL⁻¹) under the 980 nm excitation with power intensity of 0.08 W cm⁻² simultaneously. The inset shows the absorption spectrum of doxorubicin. (b) The ratio of simultaneous green and red emission intensity.

Fig. 6. (a) Evolution of the fluorescence intensity of core/shell UCNPs with the same concentration at different time points under 980 nm-excitation with power intensity of 0.08 W cm⁻². (b) The ratio of green and red emission intensity at the different time points.

Fig. 7. UC luminescence spectra of NaGdF₄:18% Yb³⁺,2%Er³⁺@NaYF₄ core/shell particles in the with different concentrations of Dox. (a) 20 μg mL⁻¹; (b) 50 μg mL⁻¹; (c) 70 μg mL⁻¹; (d) 100 μg mL⁻¹ at 980 nm-excitation under different laser powers.

Fig. 8. Comparison of residual detection of doxorubicin using a UCNPs probe with that using conventional methods. (a) UCNPs probe insertion into blood vessels at 0.15 mm (b) the traditional method was used to detect Dox insertion into blood vessels at 0.15 mm. (c) The traditional method was used to detect Dox insertion into blood vessels at 0.25 mm.