Synthesis And Bioapplications Of Rare-earth Naomaterials

Rare-earth nanomaterials are a class of materials with excellent light and chemical stability,narrow emission peaks,and long fluorescence lifetimes.Their applications in the biomedical field have gradually become research hotspots such as bioimaging,biodetection,drug delivery,disease treatment,and so on.Their applications for diagnosis and treatment of tumor are very promising.However,due to the inherent narrow absorption cross section of rare-earth ions,the utilization efficiency of the excitation light is greatly limited.In order to achieve an ideal imaging or therapeutic effect,the strategies of increasing the dosage of nanoparticles,the power density of the excitation light,or the exposure time have been widely used,which undoubtedly significantly increases the issues of biosafety and stability of rare-earth nanomaterials.Therefore,tuning the intrinsic properties of rare-earth nanomaterials(e.g.fluorescence)has become an important and urgent problem to be solvedFluorescence resonance energy transfer(FRET)and direct electron transfer(DET)are the process in which the excited state energy is transferred from a donor to the acceptor through a non-radiative transition,which can excite the acceptor to emit fluorescence.Therefore,using a near-infrared dye with a wide absorption cross section to sensitize rare-earth nanomaterials has been an important strategy for overcoming the narrow absorption of rare-earth ions to improve their fluorescence for biomedical application.In this thesis,we first investigated the synthesis and characterization of rare-earth nanomaterials with Nd3+ and Tm3+ emission centers,and then used near-infrared organic dye(IR-808)to sensitize rare-earth nanomaterials and improve their fluorescence.We finally used the modified nanomaterials to achieve the goals of diagnosis and treatment of gliomas with near-infrared Ⅱ fluorescence(NIR-Ⅱ)imaging and gas therapy.The thesis consists of three chapters.Chapter 1:A brief overview on the development and advances of rare-earth nanomaterials was summarized to demonstrate the background and significance of current research in this thesis.Chapter 2:This chapter reports the synthesis of core-shell NaNdF4@NaLuF4 nanoparticles,the modulation of their second near-infrared(NIR-Ⅱ)fluorescence,and their application for NIR-Ⅱ fluorescence imaging of orthotopic gliomas.Under 808 nm laser irradiation,the fluorescence of synthesized core-shell nanoparticles at 1340 nm was 2.5 times higher than that of NaNdF4 core.After modification with a near-infrared organic dye IR-808,the fluorescence of core-shell nanoparticles at 1340 nm was further increased by 10 times,which makes this often neglected 1340 nm fluorescence applicable.The resultant bright nanoparticles were used to diagnosis of orthotopic gliomas through the NIR-Ⅱfluorescence imaging,after the opening of blood-brain barrier of mice under the combined treatment of ultrasound and microbubbles.Chapter 3:This chapter shows the synthesis of core-shell NaYF4:Yb/Tm@NaYF4:Nd nanoparticles.Under the irradiation of 808 nm excitation,the nanoparticles can simultaneously exhibit the down-conversion and up-conversion luminescence.We used the dye sensitization strategy to further improve the characteristic emissions of Tm3+at 348 nm and 365 nm to stimulate the release of more SO2 molecules from the light-responsive prodrug(ATD),which resulted in oxidative stress and inhibition of the autophagy of cancer cells,resulting in the apoptosis of tumor cells.At the same time,dye sensitization can also lead to the enhancement of the NIR-Ⅱ fluorescence of core-shell nanoparticles at 1340 nm,which can be used for NIR-Ⅱ fluorescence imaging of the subcutaneous and orthotopic gliomas.These results make the rare-earth nanoparticles more attractive in the diagnosis and treatment of glioma.