Preparation And Surface Functionalization Of NaYF₄:Yb,Tm@SiO₂@TiO₂/Au Nanoparticles And Their Application In Spect Imaging

Nowdays,cancer.has become the most serious disease that threatens human life.Although different kinds of cancers may have various causes and tumors may grow in different tissues at different location,most of them show indescribable clinical symptoms.It is very difficult to make a definite diagnosis at the earlier stage in these diseases.Consequently many cancer patients missed the best treatment period.Early diagnosis and effective treatment of cancer is an urgent problem to be solved in clinical medicine.Photodynamic therapy(PDT)as a traditional anti-cancer treatment has been used in clinical medicine for a long time due to the advantages of good safety,low toxicity and less side effects,no drug resistance and so on.In the PDT treatment,a photosensitizer(PS)was administrated into the cancer tissue and then exposed to irradiation of light with specific wavelength.It can produce the cytotoxic reactive oxygen species(ROS)to achieve cancer cell apoptosis.Some nano-sized inorganic photosensitive drugs constructed by using rare earth upconversion luminescence nanoparticles(UCNs)can be used for a PDT treatment in deep tissue under irradiation of near-infrared light(NIR).And introduction of photocatalysts like TiO2 into UCNs-contained PS drugs can further overcomes the disadvantages of easy deactivation of the organic photosensitizer.At the same time,the UCNs-contained PS drugs can also be used as optical imaging,magnetic resonance imaging(MRI),X-ray tomography(CT),or dual/multi-modal imaging probes for tumor detection due to the properties of rare earth ions,such as luminescence,magnetism,strong X ray absorption ability,etc..In this dissertation,a new PDT nanodrug containing UCNs,silica,titanium dioxide and gold was constructed.Surface modification and functionalization of this drug with a ligand and a chelating agent were studied,and the feasibility of using it as a single-photon emission computed tornography(SPECT)imaging probe was discussed.The detailed research contents and results are as follows:(1)NaYF4:Yb,Tm nanoparticles with a diameter of about 25 nm was prepared by high temperature solvothermal method,followed by successively coating with SiO2 and TiO2 layers by using reverse microemulsion method and controlled hydrolysis method respectively to prepare UCNs@SiO2@TiO2 nanoparticles with different sizes.Then gold nanograins were photochemically deposited on the surface of the nanoparticles.After optimization of the reaction system,UCNs@SiO2@TiO2 decorated with controllable Au nanograins in size and density were prepared by changing the irradiation time and the amount of gold precursor.UCNs@SiO2@TiO2/Au showed much higher photocatalytic activity in degradation of the model molecule rhodamine B(RhB)under the excitation of 980 nm laser than UCNs@SiO2@TiO2,which is expected to be a PDT drug with enhanced activity in the treatment.(2)Study on surface modification of UCNs@SiO2@TiO2/Au via Au-S bond was conducted.arginine-glycine-aspartic acid peptide(RGD),a ligand specifically targeting to integrin ?v?3 overexpressed on angiogenic tumor blood vessels,and the chelating agent diethylene triamine pentacetate acid(DTPA)were coupled to the PDT drug.The composition,size,surface potential,absorption spectrum and dispersion stability of the targeted PDT drug UCNs@SiO2@TiO2/Au-RGD-DTPA were characterized by infrared spectroscopy,dynamic light scattering,zeta potential analysis,UV-Vis spectra etc..The targeted drug is able to chelate Gd3+ firmly to form UCNs@SiO2@TiO2-RGD/DTPA-Gd3+,which may be a perspective MRI T1 contrast agent for tumor imaging.Furthermore,UCNs@SiO2@TiO2/Au-RGD-DTPA can bind radioactive 99mTc with a fairly high labeling yield of over 90%,with the help of DTPA.In vivo Single-photon emission computed tomography(SPECT)imaging experiment was performed by intravenous injection of UCNs@SiO2@TiO2-RGD/DTPA-99mTc into a tumor-bearing nude mice.The results proved that UCNs@SiO2@TiO2-RGD/DTPA-99mTc can be used for in vivo SPECT imaging but the drug was fail to target the tumor.Further investigation are needed to explore how to improve the drug's targeting performance.In addition,the feasibility of etching the SiO2 layer of UCNs@SiO2@TiO2/Au by different solutions was explored in this paper.The etched product containing loose SiO2 layer had an increase in adsorption capacity for rhodamine B compared with the original nanoparticle.It may be used for construction of a difunctional anti-cancer drug with NIR-triggered photodynamic therapy and chemotherapy,after loading a chemotherapeutic drug such as doxorubicin.