Rare Earth Doped NaYF₄ Core-Shell Nanoparticles For Tumor Photodynamic Therapy

Photodynamic therapy(PDT)is a kind of cancer therapy with strong specificity.However commonly used photosensitizers absorb visible lights which have poor tissue penetration ability.Therefore clinical application of PDT in deep cancer treatment is limited.Moreover,solid tumor is in a hypoxic microenvironment,which seriously affects the therapeutic effect of oxygen-consuming PDT.Upconversion luminescent nanomaterials can convert strong tissue-penetrating near infrared(NIR)light into visible or even ultraviolet light through anti-Stokes emission process,which can break through the limitations of photodynamic therapy.Specific experimental results are as follows:(1)Upconversion luminescent nanoparticles NaYF4:Yb,Er@NaYF4:Nd with good morphology and uniform size were prepared by coprecipitation method,then their microstructures and luminescent properties were characterized.Because Nd3+ is doped in the shell,it can be excited by 808 nm laser with strong tissue penetration and low thermal effect.After that,the temperature sensing performance of the core-shell nanoparticle was preliminarily explored.It is expected to play an important role in biomedicine as a new cell temperature probe,for the obvious linear relationship between ln(I540/I520)and 1/T.(2)Core-multishell upconversion luminescent nanoparticles NaYF4:Yb,Er@NaYF4:Nd@NaYF4 were prepared by coating the core-shell nanoparticle with a inert NaYF4 shell,which enhanced the luminescent intensity by inhibiting surface quenching.Then the photodynamic therapy platform was constructed by loading Ce6 and ferric hydroxide nanoparticles on the upconversion luminescent particles coated with silica core-shell structure(UCS).The Fenton-like reaction of Fe3+ can continuously produces oxygen and some reactive oxygen species(ROS)in tumor cells,which is used to alleviate hypoxia of tumors and promote the therapeutic effect of photodynamic therapy.The nanocomposite UCS-Ce6-Fe(OH)3 has good chemical stability and biocompatibility.(3)Biological characterization of the photodynamic therapeutic properties of the composites was carried out.Firstly,cytotoxicity of the nanocomposite were tested on human renal epithelial cell 293T and 4T1 mouse breast cancer cell and erythrocyte respectively.The results showed that the nanocomposite had good cell compatibility and blood compatibility.Then we validated the photodynamic effect of the granules under normal and hypoxic conditions in vitro.The results showed that a group of cells promoted by Fenton-like reaction had the best killing effect.In addition,the production of intracellular ROS under different experimental conditions was also observed by fluorescence microscopy,which supported the conclusion above.Finally,in vivo photodynamic experiments were performed on the 4T1 breast cancer model of mice to further verify the efficacy of compound particles in enhancing photodynamic response.This study provides a novel solution for building a more perfect photodynamic therapy platform.