The Synthesis And Luminescence Regulation Of A Novel Rare Earth Upconversion Nanomaterials And Its Application In Cancer Therapy

Ln³⁺ions-doped upconversion nanoparticles?UCNPs?have excellent spectral characteristics,which are generally excited by near infrared light and have deep tissue penetration depth,small light damage,good light stability,and great potential in bioimaging and bioanalytical field.In recent years,people are devoted to developing novel upconverting nanocrystals with higher luminous efficiency.Particularly,by combining with other functional materials such as photosensitizers and anti-cancer drugs,a theranostic nanoplatform based on UCNPs can been constructed,which shows superior imaging and therapeutic efficacy.In this thesis,we focus on the preparation and luminescence tuning of novel UCNPs and apply it to construct a near-infrared responsive upconversion nanoplatform against hypoxic tumors via nitric oxide enhanced photodynamic therapy:?1?.The low luminescence quantum efficiency of traditional UCNPs is mainly caused by surface defects,concentration quenching,etc.,which greatly limits its application in the biological field.In this work,we have synthesized the core-shell-shell structured UCNPs with a composition of Na YF₄:Yb@Na Yb F₄:Tm/Gd@Na YF₄ by thermal decomposition,and studied the influence of thickness of luminescent inner shell and the Yb³⁺doping in the core region on the emissive properties.The results indicate that when the inner shell thickness is about 2.8 nm and 30 mol%Yb³⁺ions are doped in the core region,the core-shell-shell UCNPs have optimal UV and blue light emission.The emission intensity of optimized core-shell-shell UCNPs is about 5 times larger than that of conventional core-shell UCNPs?Na YF₄:Yb/Tm?30/0.5%?@Na YF₄?.In addition,the deep UV upconversion emission?312 nm?can also be achieved by doping Gd³⁺.The mesoporous silica shell is further decorated on the surface of these UCNPs to render them water soluble and the surface area of obtained UCNPs@m Si O₂ is about 777 m²·g^-1.We also study the cytotoxicity and UCL imaging of UCNPs@m Si O₂ in He La cells.The results has shown that the UCNPs@m Si O₂ have no obvious toxicity,and the cell viability can reach above 95%after incubation with He La cells for 24 h.Under confocal microscopy,the obvious upconversion fluorescence in He La cells is observed,indicating that UCNPs@m Si O₂ successfully enter the cells and have good biocompatibility,which is expected with a great potential in construction of a theranostic nanoplatform based on UCNPs.?2?.Photodynamic therapy?PDT?is a well-known and effective approach of cancer treatment,but it still suffers from severe hypoxic condition of the tumor microenvironment.In this work,by incorporating PDT photosensitizer?curcumin?and NO donor?[NH₄][Fe₄S₃?NO?₇],RBS?into UCNPs,we have developed a near-infrared?NIR?activated theranostic nanoplatform based on UCNPs?UCNPs@m Si O₂-CUR-RBS?.Upon illumination with 980 nm laser light,the emitted blue and ultraviolet light by UCNPs can simultaneously activate curcumin and RBS and subsequently release¹O₂ and NO gas.NO can inhibit cellular respiration and allows for more O₂ to be available for PDT treatment,thereby achieving the NO-enhanced PDT treatment in the deep lesions.Our results suggest that the photo-released NO upon NIR illumination can greatly decrease the oxygen consumption rate and thus increase the singlet oxygen generation,which ultimately leads to an increased number of cancer cell deaths.Even under hypoxic conditions,it still shows excellent PDT efficacy and deeply inhibits tumor growth in tumor-bearing mice.It is believed that the methodology developed in this study enables to relieve the hypoxic-induced resistance in PDT therapy and also holds great potential for overcoming hypoxia challenges in other oxygen-dependent therapies.