Abstract

An organic-inorganic hybrid core-shell nanostructure, based on mesoporous silica coated upconversion core-shell nanoparticles (NaGdF4:Yb,Er@NaGdF4:Yb@mSiO2-Dopa abbreviated here as UCNP@mSiO2-Dopa) that stably incorporates dopamine (Dopa) in the silica layer was introduced as a theranostic nanoplatform for optical imaging guided photothermal therapy (PTT) using NIR excitation. Silica-attaching polyethylenimine make the Dopa transforms into an active form (transferred Dopa) that strongly absorbs light under single 980 nm irradiation. We show that the activated UCNP@mSiO2-Dopa nanoplatform is able to produce a pronounced photothermal effect, that elevates water temperature from room temperature to 41.8 °C within 2 minutes, while concurrently emitting strong upconverted luminescence (UCL) for visualized guidance under 980 nm laser. In addition, we demonstrate the application of the same UCNP@mSiO2-Dopa nanoplatform for magnetic resonance imaging (MRI) and x-ray computed tomography (CT) enabled by the gadolinium (Gd) element contained in the UCNP. Importantly, the in vitro and in vivo anti-cancer therapeutic effects have been shown efficacious, implying the use of the described nanoplatform as an effective multi-modal imaging enabled PTT agent. Results from the in vivo biodistribution of UCNPs@mSiO2, cellular live/dead assay, and histologic analysis of main organs of treated mice, reveal that the UCNP@mSiO2-Dopa agents are bio-compatible with low toxicity.

Highlights

  • Light-activated cancer treatment has attracted considerable attention, as it can allow noninvasive regulation of the therapeutic process at the intended site, with a defined manner, overcoming the commonly met side effects associated with conventional chemo-therapy[1,2,3,4]

  • Our design concept is illustrated in Fig. 1: 1) Dopa is transformed into a deprotonated form when incorporated into a mesoporous silica as the shell layer on the Upconversion nanoparticles (UCNPs) core, with the assistance of polyethylenimine (PEI). 2) The transferred Dopa could absorb the blue and green upconversion generated under 980 nm laser, and the unabsorbed red upconversion luminescence (UCL) from the UCNP provides optical imaging and tracking capability

  • The X-ray diffraction (XRD) pattern of the as-synthesized UCNP@mSiO2-Dopa is shown in Figure S1, in which all diffraction peaks can be well assigned to hexagonal NaGdF4, revealing the hexagonal crystallographic phase of the core/shell NaGdF4:18%Yb,2%Er @

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Summary

Results and Discussion

Phase, structure, shape, and luminescent properties. The XRD pattern of the as-synthesized UCNP@mSiO2-Dopa is shown in Figure S1, in which all diffraction peaks can be well assigned to hexagonal NaGdF4, revealing the hexagonal crystallographic phase of the core/shell NaGdF4:18%Yb,2%Er @. There is no apparent temperature increase in the other two solutions of PBS saline solution, PBS solution containing UCNP@mSiO2 (Fig. 6B) This indicates that the UCNP@mSiO2 without the transferred Dopa could not be used as a PTT agent. When the nanoparticle-treated HeLa cells were exposed to 980 nm irradiation for 10 min, most the cancer cells have been killed It is shown that there are no abnormal phenomena in the group treated with PTT: no damage is observed in the hepatocytes, no fibrosis appears in the pulmonary, and no concentration is found in the glomerulus Both the in vitro and in vivo results demonstrate the potential use of UCNP@mSiO2-Dopa as an effective PTT agent

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