Iron oxide decorated MoS₂ nanosheets with double PEGylation for chelator-free radiolabeling and multimodal imaging guided photothermal therapy

Theranostics for in vivo cancer diagnosis and treatment generally requires well-designed nanoscale platforms with multiple integrated functionalities. In this study, we uncover that functionalized iron oxide nanoparticles (IONPs) could be self-assembled on the surface of two-dimensional MoS₂ nanosheets via sulfur chemistry, forming MoS₂-IO nanocomposites, which are then modified with two types of polyethylene glycol (PEG) to acquire enhanced stability in physiological environments. Interestingly, ⁶⁴Cu, a commonly used positron-emitting radioisotope, could be firmly adsorbed on the surface of MoS₂ without the need of chelating molecules, to enable in vivo positron emission tomography (PET) imaging. On the other hand, the strong near-infrared (NIR) and superparamagnetism of MoS₂-IO-PEG could also be utilized for photoacoustic tomography (PAT) and magnetic resonance (MR) imaging, respectively. Under the guidance by such triple-modal imaging, which uncovers efficient tumor retention of MoS₂-IO-(d)PEG upon intravenous injection, in vivo photothermal therapy is finally conducted, achieving effective tumor ablation in an animal tumor model. Our study highlights the promise of constructing multifunctional theranostic nanocomposites based on 2D transitional metal dichalcogenides for multimodal imaging-guided cancer therapy.