Some Scientific Problems On Upconversion Photodynamic Therapy Based On Rare Earth Doped NaYF₄ Nanocrystals

Upconversion photodynamic therapy（UC-PDT）has gained considerable interest in the biomedical field.Rare-earth nanocrystals（RE-NCs）can convert near-infrared light to UC visible light,and the produced visible light can further activate photosensitizers to produce reactive singlet oxygen and kill tumor cells.PDT using RE-NCs displays enhanced treatment depth,since that the near-infrared light penetrates deeply into the biologic tissues.This UC-PDT shows great promise in solid tumor treatment,such as liver cancer,and represents a major breakthrough compared to the traditional PDT.However,there are still some obstacles hindering the practical application of UC-PDT.The synthesis method of RE-NCs need optimization;The influence of the environment on the UC luminescence lacks enough understanding;The heating effects of pump laser on tissues need to be evaluated accurately.Based on this background,correlative scientific problems about UC-PDT based on rare erath doped NaYF₄ NCs were investigated in this paper.The preparation method of rare-earth doped NaYF4 bare core and homogeneous core-shell nanocrystals（NCs）with high upconversion luminescence efficiency was investigated.Small（<50 nm）,mono-dispersed,hexagonal-phase NaYF4: Yb,Tm bare core NCs with adjustable morphology was synthesized using a friendly method by adjusting the reaction time,temperature and oleic acid（OA）concentration.Then,a one-step seed-mediated method was invented to synthesize homogeneous core-shell NCs with highly tunable and uniform thickness shells.It was determined that the quantity of ligand OA directly affects the uniformity of shell precursor epitaxial growth on core NCs.The optimum quantity of ligand OA was experimentally determined.Based on this finding,NaYF₄: Yb,Tm/NaYF₄ core-shell NCs with shell thicknesses tuned to 1 nm,3 nm,5 nm,10 nm,and 15 nm were synthesized.TEM and EDS analysis confirmed the successful synthesis of core-shell NCs with the aforementioned specifications.The UC fluorescence enhancement of NaYF₄: Yb,Er NCs by core-shell structure was investigated.The correlation between shell thickness and UC luminescence intensity of NaYF₄: Yb,Er/NaYF₄ core-shell nanocrystals was investigated experimentally and theoretically.We found that the UC fluorescence intensity of the core-shell nanocrystals was enhanced exponentially with shell thickness.The “optimized shell thickness” was defined to balance the conflict requirements of strong UC fluorescence intensity and small total crystal size for bio-applications.The feasibility of the practical application of this NaYF₄: Yb,Er/NaYF₄ core-shell structure with optimal shell thickness was verified by the related biological experiment.Accurate thermometry based on NaYF₄: Yb,Er NCs was studied.A biological temperature measurement way based on fluorescence intensity ratio（FIR）was developed to reduce uncertainty.The upconversion luminescence of NaYF₄: Yb,Er nanocrystals were studied as a function of temperature around physiologically relevant range of 300 K–330 K.We found that the green-green FIR（I521/I540）and red-green FIR（I654/I540）varied linearly as temperature increased.The thermometric uncertainties using the two FIRs were discussed and determined to be almost constant at 0.6 and 0.09 K for green-green and red-green,respectively.The lower thermometric uncertainty comes from the intense signal to noise ratio of the measured FIR owing to their comparable fluorescence intensities.