Abstract
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.
Highlights
Radiation therapy (RT), which is one of the clinically used cancer treatment strategies, in addition to chemotherapy and surgery, utilizes ionizing radiation (X-ray or γ-ray radiation) to ablate tumors without depth restriction.[1,2,3] during RT, only a small fraction of radiation energy is absorbed by tumor cells, whereas normal tissues within the path of the radiation beam are affected in a non-selective manner
nanoscale metal-organic particles (NMOPs) composed of metal ions and IR825 ligands were fabricated in a mixed solvent of DMF and methanol via the post-synthesis cation exchange method (Figure 1a)
Mn-IR825 NMOPs were synthesized after addition of IR825 into a solution of manganese chloride dissolved in methanol/DMF (V/V: 85/15) at 30 °C
Summary
Radiation therapy (RT), which is one of the clinically used cancer treatment strategies, in addition to chemotherapy and surgery, utilizes ionizing radiation (X-ray or γ-ray radiation) to ablate tumors without depth restriction.[1,2,3] during RT, only a small fraction of radiation energy is absorbed by tumor cells, whereas normal tissues within the path of the radiation beam are affected in a non-selective manner. Starting from our previously reported Mn-IR825 NMOPs as nanotemplates, we fabricated both core-shell and co-doped Mn/Hf-IR825 NMOPs via a post-synthesis cation exchange method and exploited these NMOPs as radiosensitizers and photothermal agents for the combination of PTT and RT. In this nanostructure, Mn2+ ions are used as a contrast agent for T1-weighted MR imaging; IR825, with strong NIR absorption, is used as an excellent contrast agent for photoacoustic (PA) imaging and a photothermal agent for PTT; and Hf4+, with a high-Z number, offers contrast for X-ray computed tomography (CT) imaging and endows NMOPs with strong X-ray absorbance for enhanced RT. Our work presents a facile post-synthesis cation exchange method to synthesize core-shell and co-doped NMOPs that can act as biodegradable and versatile nanoplatforms with highly integrated biomedical imaging and therapy functions
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