Design And Application Of Rare Earth Fluoride With Core-Shell Structure For MRI/CT/UCL Multi-Mode Imaging

Nanomaterials have become an important role in the field of biological imaging and clinical diagnosis because of its unique advantages such as controllable synthesis,easy modification,facile integration of different functionalities.We can integrate different imaging functions into one nanoplatform through reasonable design.It is important to combine merits of different imaging modes and construct multimode imaging probe,which can provide more comprehensive diagnostic information and track the process of disease.Lanthanide-based upconversion nanoparticles have potential applications in clinical diagnosis and treatment because of their excellent biocompatibility,easy regulation of particle size and morphology.In recent years,MR and CT dual-mode imaging probe is more extensive,but this kind of probes still have a common limitation,they have low resolution for cell.The combination of MRI,CT and optical imaging can solve this problem because these probes not only have excellent tissue penetrating ability,but also achieve high resolution three-dimensional tissue structure imaging and cellular imaging.Therefore,we chose lanthanide nanoparticles as matrix to design a new nanoprobes for MRI,CT and optical imaging.Herein,we synthesized the NaYbF₄:Tm@NaGdF₄:Yb with uniform particle size by the pyrolysis method on the basis of the paramagnetism of Gd,the K-edge binding energy?61 KeV?of Yb and its unique electronic structure.The hydrophobic OA stabilized nanoparticles were converted into hydrophilic nanoparticles through the ligand exchange with PVP,which is necessary for using as NIR-NIR UCL,T₁-weighted MRI and CT multimodal imaging probes.The composition and morphology of NaYbF₄:Tm@NaGdF₄:Yb-PVP were studied by transmission electron microscopy?TEM?,X-ray diffraction?XRD?,X-ray photoelectron spectroscopy?XPS?and Fourier transform infrared spectroscopy?FT-IR?.The cytotoxicity of NaYbF₄:Tm@Na Gd F4:Yb-PVP against HeLa cells and 4T₁ cells was evaluated by MTT assay.When incubation period was 24 h,the cell viability were still above 80% even at a higher concentration of 500 ?g Yb/mL,which indicated the relatively low cytotoxicity of NaYbF₄:Tm@NaGdF₄:Yb-PVP.The histological assessment results showed that the NaYbF₄:Tm@NaGdF₄:Yb-PVP could cause any tissue damage,inflammation or lesion to mice.These nanoprobes exhibited a desirable longitudinal relaxivity?r1=3.58 mM-1 s-1?and strong X-ray attenuation property?58.84 HU L g-1?.The NIR emission intensity of NaYbF₄:Tm@NaGdF₄:Yb-PVP is approximately 60 times higher than that of the NaYF4:Yb/Tm.Furthermore,the NIR-NIR UCL/MRI/CT imaging in vivo showed a significant signal enhancement in liver and spleen after injection,which indicated that the NaYbF₄:Tm@NaGdF₄-PVP could serve as NIR-NIR UCL,T₁-weighted MRI and CT multimodal imaging probes.More importantly,the detection of small tumor was successfully achieved after intravenous injection.These results revealed that NaYb F4:Tm@NaGdF₄:Yb-PVP UCNPs could serve as promising NIR-to-NIR UCL/MRI/CT trimodal imaging probes.