Application of Er3+Ion Doped Rare Earth Fluoride Multifunctional Nano-Fluorescence Probe in Precision Tumor Theranostics

Author:Yu Zhang Sen

Supervisor:wu ai guo

Database:Doctor

Degree Year:2018

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Pages:162

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Rare earth doped upconversion nanoparticles(UCNPs)have been widely used in solar photoelectric conversion,optical information technology,biomedicine and optoelectronics due to their unique luminescent properties.Especially in the field of biomedicine,after surface functional modification of UCNPs,in depth researches have been conducted on biomedical imaging,biomarker detection,drug delivery,disease diagnosis and treatment,and some outstanding results have been achieved.However,there are also problems such as low upconversion luminescence quantum yield,fixed excitation wavelength and biosafely in UCNPs design,construction and biomedical applications.This thesis mainly focuses on the design and construction of Er3+doped fluoride multifunctional nano-fluorescent probes and its application in the precise tumor theranostics,and explores possible solutions to above problems.The main research content is summarized as follows:(1)LiLuF4:Yb,Er was selected as the upconversion luminescence core to constructed an untrasmall size upconversion fluorescence multifunctional nanoprobe MNPs(MC540)/DSPE-PEG-NPY with particle size less than 25 nm,which has targeted upconversion fluorescence,MR,CT imagings and photodynamic therapy(PDT)functions,and the NPY target molecule increases the amount of nanoparticles enriched at the tumor site by a factor about two.The experimental results show that durging the nanoprobe synthesis process,the epitaxial growth of multilayer LiGdF4thin shells by high temperature coprecipitation method,which increased the fluorescence intensity of the luminescent core by 5.4 times,and the longitudinal and transverse relaxation rates were r1=10.24 mM-1s-1,r2=16.44 mM-1s-1,CT imaging evaluation parameter value was 20.97 HU·mg-1·mL.The ultrasmall structure of UCNPs and the covered of DSPE-PEG shell with good biocompatibility both are effective in reducing in vivo acute toxicity of the multifunctional probe.When the injection dose is less than 200 mg/kg,the multifunctional nanoparticles have no obvious toxicity.Therefore,the probe can achieve excellent targeted trimodality imaging and PDT effects.(2)Based on the multi-energy levels absorption features of Er3+,the single erbium doped nanoparticles(SED)with multi-wavelength excitation and up/down conversion fluorescence were obtained by single doping of Er3+in 12 rare earth fluoride hosts.The SED nanoparticles were characterized by TEM,XRD,visible-near infrared absorption spectra,and up/down conversion fluorescence spectra.The Judd-Ofelt theory was used to calculate the spectral parameters of some of the levels of Er3+doped in rare earth fluoride hosts.The oscillator strength parametersΩt(t=2,4,6),spontaneous radiative transition rates Arad,fluorescence branching ratioβ,and the spontaneous radiative transition lifetimeτSR were obtained.The influence of the SED nanoparticles properties on the luminescence intensity was analyzed.This work lays the foundation for the exploration of multi-wavelenght excitation of highly efficient luminescent nanoparticles.(3)NaLuF4 host was selected for Er3+and Gd3+codoping to construct SED nanoparticles.Gd3+ion doping was used to adjust the SED nanoparticles size.When the Gd3+doping concentration was from 0.0%to 20.0%,the SED nanoparticles size was reduced from 213 nm to 43 nm.The longitudinal and lateral relaxation rates of SED nanoparticles were r1=2.79 mM-1s-1,r2=3.34 mM-1s-1,and the CT imaging evaluation parameter value was 16.52 HU·mg-1·mL.The use of epitaxially grown multilayer NaLuF4 inert shells to increase the fluorescence intensity of the luminescent core by 7.3-fold;further use of DSPE-PEG for surface modification and for in vivo up/down conversion fluorescence imaging with 808,980 and 1530 nm laser excitation and evaluation of the effects of imaging with different excitation and fluorescence bands;evaluation of acute toxicity of SED nanoparticles in vivo.SED nanoparticles have no obvious toxicity when the injection dose is less than 100 mg/kg.The SED nanoparticles constructed by this work realizes visible and near infrared region I and II region fluorescence imaging in multi-wavelength excitation and has good biological safely,which is great significance to the development of biomedical fluorescence imaging.In summary,the research work in this thesis is based on the rare earth upconversion fluorescence nanoparticles constructd the multifunctional nano fluorescence probe provide methods and techniques for precise tumor theranostics.In the design and construction of multifunctional nano fluorescent probes,biosafety was improved by reducting the size of probes and coating DSPE-PEG;multilayered shell structure was obtained by single doping and epitaxial growth of Er3+.The method achieves strong up/down conversion luminescence of SED nanoparticles under multi-wavelength excitation.The research results of this dissertation have certain positive significance for promoting the application research of UCNPs in the biomedical field.