Preparation Of Nd³⁺ Sensitized Upconversion Nanoparticles And Study On Light-Controlled Release Of NO

Up-conversion nanoparticles(UCNPs)generate upconverted ultraviolet and visible light through the continuous absorption and energy transfer of photons by rare earth ions.Benefiting from its long life,good stability,low toxicity,weak fluorescence background and large penetration depth,it has been widely used in the fields of biological detection,biological imaging,drug delivery and photodynamic therapy.Nitric oxide(NO)is one of the smallest structural drug molecules,which has potential therapeutic effects in regulating vascular tone,anti-cancer,antibacterial,and wound healing.At low concentrations,it can relax blood vessels in the cardiovascular system,and at high concentrations,it can directly kill cancer cells.Folic acid(FA)is a small molecule vitamin.Animal cells can only rely on the folate receptor on the cell surface to take in exogenous folic acid to maintain normal life activities.The number and activity of folate receptors in most tumor cells far exceed those of normal cells.Therefore,up-conversion nanoparticles can be modified with FA,which can be used as a fluorescent probe for tumor targeting.This thesis used rare earth up-conversion nanoparticles as the carrier,and two main tasks have been performed.One is based on the up-conversion luminescence design of up-conversion nanoparticles,a nano system that releases NO under the induction of 808nm near-infrared light was synthesized;The other is by modifying the surface of up-conversion nanoparticles,a FA-modified potential fluorescent probe targeting tumor was synthesized.The main results of this research are divided into the following three parts:(1)NaYF₄ naked nucleus with Tm³⁺as the activator was synthesized by solvothermal method.With Ca OA as the calcium source,10%Ca²⁺was doped into the NaYF₄ lattice to further increase the fluorescence intensity of the naked nucleus,then used the seed method to coat a layer of active NaGd F₄ shell on the surface of the bare core.The optimal doping ratio of Nd³⁺and Yb³⁺in the shell layer was discussed,and Nd³⁺-sensitized UCNPs with excellent luminescence were synthesized.Finally,the surface modification of mesoporous silica transforms UCNPs from hydrophobic to hydrophilic,and has the ability to load drugs,which provides a good carrier for NO donors and other drugs.(2)S-nitroso-N-acetylpenicillamine(SNAP)was synthesized according to literature reports,which absorbed ultraviolet light and then loaded on UCNPs@m Si O₂.Based on the principle of fluorescence resonance energy transfer(FRET),the ultraviolet light was emitted by the up-conversion transfers energy to the NO donor to effectively release NO.The Griess reagent was used to detect the released NO.Finally,the CCK-8 method was used to evaluate the biological toxicity of the NO release system to liver cancer cells.The results show that the cytotoxicity of the complex was low without 808 nm laser irradiation.The NO released by 808 nm laser irradiation for 10min caused a large number of liver cancer cells apoptosis.(3)NaYF₄ with Er³⁺as the activator was synthesized by solvothermal method,and the optimal doping concentration of Er³⁺was discussed.The NaYF₄ core with uniform morphology,good crystallization and high fluorescence intensity was successfully prepared,and then the surface of the bare core was coated with the seed method.Covering a layer of Nd³⁺-sensitized NaYF₄ shell layer,and then modifying the surface of UCNPs with silica,amino modification and covalent grafting with folic acid to synthesize 808 nm excited UCNPs emitting yellow-green light.It can be used as a potential fluorescent probe for tumor targeting.