Core-shell and co-doped nanoscale metal-organic particles (NMOPs) obtained via post-synthesis cation exchange for multimodal imaging and synergistic thermo-radiotherapy

Nanoscale metal-organic particles (NMOPs) have recently shown great promise in the area of nanomedicine owing to their tunable compositions, highly enriched functionalities, well-defined sizes/shapes and intrinsic biodegradability. Herein, we describe the fabrication of NMOPs with both core-shell and co-doped structures via a post-synthesis cation exchange method for applications in multimodal imaging and combined photothermal and radiation therapy of cancer. Template NMOPs containing Mn2+ and IR825, a near-infrared (NIR) dye, are first synthesized and then mixed with Hf4+ to obtain core-shell and co-doped Mn/Hf-IR825 NMOPs depending on the dose of added Hf4+ ions. In these NMOPs, Mn2+ offers strong T1 magnetic resonance (MR) contrast, Hf4+ is a high-Z element with excellent computed tomography signal enhancement ability and radio-sensitization capability, and IR825 exhibits rather high NIR absorbance. After coating with polydopamine (PDA) and further conjugation with polyethylene glycol (PEG), the co-doped Mn/Hf-IR825@PDA-PEG particles (NMOP-PEG) showed efficient tumor-homing ability after intravenous injection, as illustrated by MR and photoacoustic (PA) imaging. Utilizing NMOP-PEG achieved excellent tumor killing efficacy through in vivo photothermal and radiation synergistic therapy in our mouse tumor model experiments. Importantly, our NMOP-PEG showed no appreciable toxicity to the treated mice and could be efficiently excreted. Our work presents a facile method to fabricate NMOP-PEG with multi-component structures as a biodegradable, multifunctional nanoplatform for multimodal image-guided combination cancer therapy.