The Study Of Controllable Preparation,Performance Control And Application Of Optical/magnetic Multifunctional Rare Earth Fluoride Nanomaterials

In recent years,the rare earth luminescent nanomaterials,as a new generation of nano-fluorescent probes,have attracted much attentions in the fields of optics and bio-imaging because of the special physic-chemical properties including narrow-band luminescence peaks,low autofluorescence,small bio-light damage,high optical and chemical stability,and signal-to-noise ratio.In particular,the rare earth fluoride nanomaterials have been successfully applied in optical communication,biological imaging,early diagnosis and treatment of tumors due to their high refractive index,low phonon energy and low requirements of preparation process.Among the existing tumor imaging detection methods,X-ray computed tomography?CT?imaging,magnetic resonance?MR?imaging and optical imaging are more favored by researchers because of their respective advantages.As we all known that the high sensitivity of optical imaging enables the realization of information detection on biological tissues and even cells,but the lack of low spatial resolution and depth of tissue penetration hinder its wide applications,which can be achieved and complemented by CT imaging with deep tissue penetration and high resolution features of MR imaging.Therefore,the construction of multi-functional nanoprobes integrating optical,CT and MR imaging functions with high efficiency and high sensitivity will help to improve the accuracy of disease diagnosis and even the early detection of tiny tumors.In addition,compared with the traditional chemotherapy,radiation therapy,surgery and other treatments,the photothermal therapy,as a new generation of minimally invasive treatment of tumors,possesses the advantages of sensitivity,high efficiency and low side effects,which makes the treated mothed widely concerned by researchers in the cancer oncotherapy.Based on the above statement,this thesis aims to construct the multi-functional rare earth fluoride nanomaterials with controllable structure and adjustable performance for single-mode/multi-modal bioimaging and tiny tumor detection applications.Then the dopamine hydrochloride?PDA?photothermal agent was grafted to rare earth fluoride nanomaterials through one-step modification,which makes the rare earth fluoride nanocrystal with photothermal function.Therefore,the successful construction and application of a multi-functional nano-therapy platform integrating with imaging and therapy abilites was successfully achieved.The main research contents and results of this thesis are as follows:?1?Different content of Mn²⁺doped NaYF₄ upconversion nanocrystals were successfully prepared by hydrothermal method with polyethylene glycol?PEG?as surface agent.The structure,phase,size and luminescence properties of the nanocrystals were systematically studied.The results show that the Mn²⁺doping can not only realize the change of NaYF₄ nanocrystalline phase but also the controlling of luminescent color.Further studies have shown that Mn²⁺doping can also increase the red and green emission intensity ratio of NaYF₄ nanocrystals,and the ratio has increased from 1.79 to 10.71.?2?The monodisperse BaYbF₅:Gd/Er upconvertion nanocrystals were successfully prepared by the simple oleic acid hydrothermal method.After the conversion of nanocrystal from oil-soluble to water solubility by hydrochloric acid treatment,the nanoprobes was successfully applied into biological imaging.Upconversion optical bioimaging shows that BaYbF₅:Gd/Er upconversion nanocrystals can be used as ideal biooptical imaging nanoprobes.In vivo CT imaging results indicate that the nanocrystal is also a good CT contrast agent.In vitro T₁ weighted MR imaging result shows that the nanocrystal has a relatively large longitudinal relaxation value(1.053 mM^-1s^-1),which reveals that the nanocrystal was suitable for T₁ weighted MRI bioimaging.Therefore,the nanocrystal can successfully realize the multifunctional bioimaging.?3?Different Tb³⁺doped NaYF₄:Gd nanorod scintillators excited by X-ray were successfully constructed,and their luminescent properties,principle and application were well studied.The results demonstrate that the emission intensity of the nanocrystalline scintillator were closely related to the doping concentration of Tb³⁺,the excitation power and the irradiation time of X-ray.The concentration of 15%Tb³⁺is optimally doped content of the nanocrystal scintillators and the luminescence intensity is positively correlated with the excitation power and radiation time of X-ray.This X-ray excited nanocrystal scintillators will help promoting the development of the deeper tissue bioimaging and photodynamic therapeutic applications.?4?Water-soluble NaLuF₄:Gd/Nd nanorods were successfully prepared by the using of polyacrylic acid?PAA?modification mothed.The crystal phase,size,morphology and luminescence properties of the nanocrystals with the change of Nd³⁺doping concentration were detailly investigated,and the nanocrystals were successfully applied in tiny tumor detection,abdominal and brain vascular imaging,and X-ray imaging.?5?The core-shell structure nanomaterials integrated with imaging and treatment functions were successfully constructed by grafting dopamine hydrochloride?PDA?onto the rare earth fluoride nanocrystal.The crystal phase and morphology of the material were systematically investigated.Optical/thermal properties and biotoxicity testing of the nanomaterials were also well studied.The multifunctional application of abnormal vessel detection and PTT treatment of tumors based on the synthetic core-shell structure nanomaterials were successfully achieved.