Bottom-Up Synthesis of Metal-Ion-Doped WS<sub>2</sub> Nanoflakes for Cancer Theranostics

Abstract

Recently, two-dimensional transition metal dichalcogenides (TMDCs) have received tremendous attention in many fields including biomedicine. Herein, we develop a general method to dope different types of metal ions into WS<sub>2</sub> nanoflakes, a typical class of TMDCs, and choose Gd<sup>3+</sup>-doped WS<sub>2</sub> (WS<sub>2</sub>:Gd<sup>3+</sup>) with polyethylene glycol (PEG) modification as a multifunctional agent for imaging-guided combination cancer treatment. While WS<sub>2</sub> with strong near-infrared (NIR) absorbance and X-ray attenuation ability enables contrasts in photoacoustic (PA) imaging and computed tomography (CT), Gd<sup>3+</sup> doping offers the nanostructure a paramagnetic property for magnetic resonance (MR) imaging. As revealed by trimodal PA/CT/MR imaging, WS<sub>2</sub>:Gd<sup>3+</sup>-PEG nanoflakes showed efficient tumor homing after intravenous injection. <i>In vivo</i> cancer treatment study further uncovered that WS<sub>2</sub>:Gd<sup>3+</sup>-PEG could not only convert NIR light into heat for photothermal therapy (PTT) but also enhance the ionizing irradiation-induced tumor damage to boost radiation therapy (RT). Owing to the improved tumor oxygenation after the mild PTT, the combination of PTT and RT induced by WS<sub>2</sub>:Gd<sup>3+</sup>-PEG resulted in a remarkable synergistic effect to destroy cancer. Our work highlights the promise of utilizing inherent physical properties of TMDC-based nanostructures, whose functions could be further enriched by elementary doping, for applications in multimodal bioimaging and synergistic cancer therapy

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