Upconversion-Magnetic Carbon Sphere for Near Infrared Light-Triggered Bioimaging and Photothermal Therapy

Abstract

Nanoparticle-based theranostics combines tumor imaging and cancer therapy in one platform, but the synthesis of theranostic agents is impeded by chemical groups on the surface and the size and morphology of the components. Strategies to construct a multifunctional platform for bioimaging and photothermal therapy (PTT) are urgently needed. A new upconversion-magnetic agent (FeCUPs) based on hollow carbon spheres, which is both a photothermal agent and a dual carrier of luminescent and magnetic nanoparticles, provides an effective approach for tumor elimination. Methods: The morphology of FeCUPs was characterized for the construction and size adjustment of the theranostic agent using transmission electron microscopy, high-resolution transmission electron microscopy, energy dispersive spectroscopy and high angle annular dark field scanning transmission electron microscopy. The distribution of FeCUPs was tracked under in-situ upconversion luminescence (UCL) imaging and magnetic resonance imaging (MRI) in vivo. Photothermal therapy was carried out on tumor-bearing mice, after which the toxicity of PTT was evaluated by a blood biochemistry test and histological section analysis. Results: Stable and uniform loading of luminescent nanocomposites on three-dimensional carbon materials is reported for the first time. Based on the mechanism of synthesis, the size of the hybrid particles was adjusted from micrometers to nanometers. External magnetic field-enhanced photothermal therapy with multi-model imaging was accomplished using FeCUPs. Moreover, no cancer recurrence was found during 14 days of recovery without PTT. Conclusions: Hollow carbon spheres, photothermal agents loaded with upconversion nanoparticles inside and magnetic nanoparticles outside were prepared for photothermal therapy. The aggregation of FeCUPs in tumors by the local magnetic field was verified by MRI and UCL imaging, and PTT was enhanced.

Keywords: carbon; hollow; magnetic; photothermal therapy; upconversion.

Scheme 1

Schematic illustration of the synthesis process of FeCUPs, and near-infrared light triggered bioimaging and photothermal therapy.

Figure 1

The morphology and structure characterization. TEM images of FeCU (A-C) with different diameters, (D) FeCU with more amount of loading Fe₃O₄. (E) TEM image of FeCUPs. (F) HRTEM of FeCU. (G) EDS line scan of Fe element in FeCU, and corresponding STEM-HAADF image. (H) STEM-HAADF image of FeCU and (I) corresponding element mapping of Yb (orange), Tm (yellow), Gd (blue), Fe (magenta), C (red).

Figure 2

Functional properties analysis. (A) T₂-weighted MRI of FeCUPs (A, upper); linear fitting with 1/T₂ and Fe concentration of FeCUPs (A, bottom). (B) Hysteresis loops of FeC loaded with different amount of Fe₃O₄, and Fe contents are 1.04wt% and 0.85wt% respectively (insect: FeC was attracted by a magnet). (C) Upconversion emission spectra of FeCUPs, UCNPs: NaGdF₄:Yb³⁺,Tm³⁺@NaGdF₄, (D) UV-Vis-NIR absorption spectra, and (E) Photo-thermal conversion curves of FeCUPs (808nm, 1.5W/cm², UCNPs: NaGdF₄:Yb³⁺,Tm³⁺@NaGdF₄).

Figure 3

Cytotoxicity in vitro and imaging in vivo. (A) Cell viabilities of HeLa cell s incubated in different conditions: control, NIR, 300 μg/L material, 300 μg/L material + NIR, 400 μg/L material, 400 μg/L material + NIR, (∗∗ = p<0.01, compared with control group, one-way ANOVA). (B) T₂-weighted MRI of mice treated with magnet and corresponding pseudo-color images. Dark circle referred to the selected area with signal decline in tumor after the injection by using FeCUPs. (C) UCL imaging of mice (upper) and CLSM image of tumor slice (bottom) under 980 nm laser irradiation. (D) Thermal images of mice under 808 nm laser irradiation.

Figure 4

Photo-thermal therapy and evaluation in vivo. (A) Tumor growth curves of different groups. (B) Photographs of excised tumors in each group after 28 days. (C) Volume of excised tumors (∗∗ = p<0.01, compared with saline group). Inset: the tumor volume of +NIR and +NIR+MF groups with minimized range of Y axis. (D) Body weights variation trend. (E) Tumor biomarkers results from blood serum biochemistry.