Preparation Of Rare Earth Doped NaYF₄ Nanocrystals And Its Applications In Temperature Sensing And Photothermal Therapy

Hyperthermia is now becoming an important treatment modality of various cancers due to its advantages of non-toxicity and no side effects.However,traditional hyperthermia methods including radiofrequency,ultrasound and microwave treatments rely on macroscopic heat sources,which cause severe side effects on normal tissues near tumors.With the rapid development of nanotechnology,particular attention has been attracted to light-activated microscopic nano-heaters.In this work,rare earth doped nanocrystal/single-walled carbon nanotubes（SWCNTs）photothermal conversion composites,i.e.,NaYF₄:Yb³⁺,Tm³⁺@NaYF₄:Yb³⁺@SiO₂-SWCNTs,were synthesized by high-temperature co-precipitation method and reversed-phase microemulsion method for the first time.SWCNTs serve as photothermal conversion agents to achieve high efficiency absorption of near-infrared radiation and photothermal conversion;NaYF₄:Yb³⁺,Tm³⁺@NaYF₄:Yb³⁺nanoparticles are optical thermal sensors to real-time monitor photothermal therapy temperature through fluorescence intensity ratio,thus achieve safe and accurate photothermal therapy.The specific research contents of this thesis are as follows:（1）NaYF₄:Yb³⁺,Tm³⁺upconversion nanoparticles（UCNPs）with uniform particle size were prepared by high-temperature coprecipitation method.The surface of UCNPs prepared by this method is hydrophobicity.To realize its application in biological systems,it is necessary to carry out hydrophilic modification research on the UCNPs.NaYF₄:Yb³⁺,Tm³⁺nanocrystals were modified by citric acid,hydrochloric acid and SiO₂ coating,respectively.The results showed that all the above three methods achieved the modification of samples from hydrophobic to hydrophilic,among which the samples coated with SiO₂ shells best retained the luminescence properties of UCNPs,and the NaYF₄:Yb³⁺,Tm³⁺samples were used for biofluorescence imaging.In addition,the temperature sensing properties of NaYF₄:Yb³⁺,Tm³⁺samples at ³F₂→³H₆（692 nm）and ³H₄→³H₆（800 nm）levels were investigated based on fluorescence intensity ratio technique.The results show that NaYF₄:Yb³⁺,Tm³⁺samples achieve maximum absolute sensitivity of 6.8×10^-4 K^-1 at 333K.Therefore,NaYF₄:Yb³⁺,Tm³⁺samples can be used as the part of real-time temperature monitoring in subsequent photothermal therapy studies.（2）NaYF₄:Yb³⁺,Tm³⁺@NaYF₄:Yb³⁺@SiO₂-SWCNTs nanocomposites were synthesized by reversed-phase microemulsion method.SWCNTs have strong intrinsic absorption in the near-infrared region,and can be used as efficient photothermal conversion agents in the nanocomposites.Core-shell upconversion particles（CS-UCNPs）NaYF₄:Yb³⁺,Tm³⁺@NaYF₄:Yb³⁺as optical thermal sensors,through the fluorescence intensity ratio of 692nm（³F₂→³H₆）and 800 nm（³H₄→³H₆）emission to achieve real-time monitoring of the temperature of nanocomposites,i.e.,eigen temperature（E.T）.Under the irradiation of 980 nm laser,the composites showed excellent photothermal conversion performance,and the temperature of the sample aqueous solution increased from 23.3℃to 60.1℃under the excitation power density of 2.9 W/cm².Further,we demonstrated in vitro photothermal conversion experiments,CS-UCNPs@SiO₂ and CS-UCNPs@SiO₂-SWCNTs samples were injected into chicken breast tissue at depths of 1 and 2mm,respectively,and the photothermal conversion properties of the nanocomposites were tested.The results show that the nanocomposites have a safe surface temperature of 36.2℃and an effective PTT temperature of 42.2℃（980 nm,2.0 W/cm²）at the injection depth of 1 mm.When the injection depth was2 mm,the eigen temperature of the nanocomposites was 45.3℃,while the surface temperature was only 39.6℃（980 nm,2.9 W/cm²）.These results provide a new idea for the design of safe and precise PTT nanocomposites.（3）NaYF₄:Nd³⁺and NaYF₄:Nd³⁺@NaYF₄:Nd³⁺nanoparticles were prepared by high-temperature co-precipitation method.In the near-infrared（808 nm）excitation,the ⁴F_3/2→⁴I_9/2transition of Nd³⁺ions achieves efficient down-conversion near-infrared emission（861 nm）.By optimizing the concentration of Nd³⁺ions in the core and shell,NaYF₄:5%Nd³⁺and NaYF₄:5%Nd³⁺@NaYF₄:12%Nd³⁺samples obtained the strongest NIR emission.Then,the temperature sensing performance of NaYF₄:5%Nd³⁺@NaYF₄:12%Nd³⁺samples was tested at the optimum doping concentration.It was found that the maximum absolute temperature sensitivity of 8.47×10^-4 k^-1 and maximum relative sensitivity of 2.52×10^-3 k^-1 at 298 K.