Preparation And Application Of Lanthanide Doped Calcium Fluoride Nanoscintillator

At present,the hot topic of clinical cancer research is the diagnosis and treatment of deep-seated tumor.The challenge lies in the development of accurate imaging and effective therapeutic and diagnostic reagents with high tissue penetration.Come ten years recently,researchers have found that nanomaterials with near-infrared two-region spectral absorption(NIR-II)can be used for photoacoustic imaging(PAI)and photothermal therapy(PTT).Nanomaterials containing high-Z elements can be used for computed tomography(CT)and radiation therapy(RT),while Gadolinium(Gd)and Iron(Fe)based nanomaterials are well suited as magnetic resonance imaging(MRI),nanomaterials doped with lanthanide elements can be used for X-ray induced photodynamic therapy(X-PDT).These nanomaterials have great potential in imaging and treatment of deep-seated tumors due to the high penetration of light sources in biological tissues.After surface modification,functional nanomaterials can be used as contrast agents for tumor imaging techniques,also used as therapeutic agents for treatment of deep-seated tumors.The purpose of this thesis is to explore the multifunctional nanosystem which can be used in deep-seated tumor imaging and treatment,and to study the new multifunctional nanosystem and its effect in deep-seated tumor imaging and treatment.The main contributions of the thesis are as follow:(1)To improve the efficiency of imaging of deep-seated tumors,we designed and synthesized Nd3+and Gd3+ co-doped Ca F2 nanoscintillator for the application of NIR-II and MRI multimode imaging.Ca F2/Nd3+(CN)、 Ca F2/Nd3+-Gd3+(CNG)nanoscintillators were prepared by using sodium citrate as a capping and coprecipitation agent through a simple hydrothermal synthesis method.The nanoscintillator emitted strong NIR-II fluorescence at 1064 nm under the excitation of808 nm laser,and performed well in the NIR-II imaging system.By introducing Gd3+into CN NPs,the Nd3+-Nd3+ cluster structure was according destroyed,and the amount of free Nd3+ was increased,resulting in great enhancement of the fluorescence intensity of NIR-II.Due to the introduction of Gd3+ into CNG structure,it also has the ability of T1 MRI contrast,and the r1 value is stronger than that of commercially available MRI contrast media.Therefore,CNG NPs can be used for dual-mode imaging of NIR-II and MRI.Further,CNG-PEG NPs has low cytotoxicity and does not cause obvious biological toxicity in dual-mode imaging system diagnosis.(2)To enhance the therapeutic effect of deep-seated tumor,we have successfully developed europium-doped calcium fluoride Ca F2/ Eu3+-PTX/VBBO(CEPV)nano platform for the synergistic treatment of X-ray-induced photodynamic therapy(X-PDT)and chemotherapy for deep breast cancer.X-PDT has great potential in the noninvasive treatment of deep tumors.CEPV is a highly sensitive multifunctional radiation sensitizer.Because the light source is X-ray,it can break through the tissue depth limitation.Ca F2/ Eu3+(CE)can effectively convert X-rays into visible light,and have a strong X-ray excitation fluorescence spectrum.The absorption spectrum of photosensitizer Victoria Blue(VBBO)is almost identical to its emission fluorescence wavelength,achieving maximum Fluorescence Resonance Energy Transfer(FRET).The selected chemotherapy drug paclitaxel(PTX)can be used as a radiation sensitizer to reduce the dose of X-rays and enhance the effect of X-PDT.Under X-ray irradiation,CEPV exhibits superior therapeutic effects than Ca F2/ Eu3+-VBBO(CEV),and these ingenious designs together contribute to the effective synergy between X-PDT and chemotherapy.Therefore,CEPV is a promising candidate drug for deep cancer treatment strategies.