Preparation And Characterization Of Rare Earth Doped Gd₂O₃/NaGd（SO₄）₂ Nanoparticles

In recent years, the rare earth ions have been extensively used in the preparation of the fluorescent material because of their wealth energy level, stable chemical properties, excellent photochemical stability, narrow-band emission and a long emission lifetime. Some inherent magnetic rare earth oxides and rare earth sulfates are ideal matrix due to the same structure that can achieve high level doping. At the same time, there are several important features of rare earth oxides and rare earth sulfates for the applications in bioimaging:superior chemical stability and photostability in vitro or in vivo, low-toxicity, adequate dispersibility in the biological environment and so on. Particularly, the excellent biocompatibilities and outstanding magnetic-optical properties have given them some new applications in biomedication and bioanalysis. Many previous studies have shown that the rare-earth ions can enhance and modify the optical performances of rare earth oxides and rare earth sulfates. Bimodal magnetic-fluorescent nanoparticles can be obtained with suitable doping type and doping ratio of rare-earth ions, and the bi-functional biomaterials can modify the fluorescence imaging and magenetic resonance imaging properties of materials in large extent which can be used as new medical imaging agents.PDT (photodynamic therapy) is a treatment of cancer performed in a non-invasive mode. When exposed to light of specific wavelength, cytotoxic reactive oxygen species (ROS) which were based on the photochemical reactions between surrounding oxygen and photosensitizers (PS) were produced to induce apoptosis of cancer cells. Since near-infrared (NIR) light was a light transparent window in the tissue, NIR is superior to traditional visible light triggered PDT, because they have deeper penetration than visible light. However, most of available PS can only be activated by visible light in the PDT, Up-conversion nanoparticles (UCNPs) therefore are the hot spot of PDT. UCNPs are anticipated to solve the problems that traditional PDT has faced, since they can convert NIR light to visible light necessary to activate the photochemical reactions of PS and kill the cancer cells.In this paper, Gd2O3 and NaGd(SO4)2 were doped with rare-earth ions respectively and bimodal magnetic-fluorescent nanoparticles were obtained. A series of tests were conducted to investigate the optical and magnetic performance of products. Cytotoxicity and photodynamic therapy performance of the prepared nanaparticles were evaluated with human cervical cancer (HeLa) cells. Taken together, the main research topics include the following two aspects.I Preparation and characterization of Yb3+ ions and Er3+ions co-doped Gd2O3 nanoparticles.Yb3+ions and Er3+ ions codoped Gd2O3 nanoparticles (Gd2O3:Yb,Er) were synthesized via a simple homogeneous precipitation method followed by a subquent heat treatment. Morphology characterization results showed that these nanoparticles were almost spherical in shape with diameters of 200-400 nm. The particles were further modified by polyethylene glycol (PEG) to improve their suspensibility and stability in water. Sintering temperature was found to greatly influence the fluoreacent properties of the products. After calcination at 700～1200℃, the Gd2O3:Yb,Er nanoparticles could emit bright up-conversion fluorescence under 980 nm NIR laser light excitation. The mechanism of up-conversion fluorescence was studied in detail, and different from many other Yb3+ ions,Er3+ ions co-doped up-conversion materials. A three-photon process was observed for both green and red up-conversion fluorescence of the Gd2O3:Yb,Er nanoparticles, the prepared Gd2O3:Yb,Er nanoparticles emitted much stronger red light than green light. The reason was investigated and ascribed to the presence of abundant hydroxyl groups on the surface of the nanoparticles as a result of PEGylation. The cells toxicity and phagocytosis results showed that Gd2O3:Yb,Er nanoparticles could be swallowed by the HeLa cells and presented low toxicity. Well-selected PDT drugs, methylene blue (MB) with a UV/Vis absorption maximum wavelength which matches well with Gd2O3:Yb,Er nanoparticles emits and 5-aminolevulinic acid (5ALA) which is a precursor of the natural PS of the natural photosensitizer phrotoporphyrin (PpIX), were loaded onto the nanoparticles respectively to obtain Gd2O3:Yb,Er-MB and Gd2O3:Yb,Er-5ALA nanoparticles. Being UCNPs, the swallowed Gd2O3:Yb,Er nanoparticles exposed to 980 nm laser light emitted red fluorescence which activated the loaded MB and PpIX, and then killed the HeLa cells via PDT mechanism. In vitro therapeutic investigation evidenced the prominent PDT effects of Gd2O3:Yb,Er-MB and Gd2O3:Yb,Er-5ALA upon NIR light irradiation. In magnetic resonance imaging (MRI) studies, the relaxivity value obtained for Gd2O3:Yb,Er was r1= 2.0475 M-1s-1 with r2/r1 ratio close to 1, suggesting that it would be a good candidates as a positive MRI agent. It is expected that these particles have promising applications in magnetic-fluorescenct biomodal imaging and NIR light-triggered PDT.Ⅱ Preparation and characterization of Tb3+ ions doped NaGd(SO4)2 nanoparticles. NaGd(SO4)2:Tb nanorods were synthesized by solvothermal method. The results show that these nanorods have a length in the range of 8～12μm approximately. The resultant NaGd(SO4)2:Tb nanorods could emit a bright blue color under the excitation wavelength of 311 nm. It was also shown that the NaGd(SO4)2:Tb could enhance the r1 relaxivity of water protons, which suggested that they could act as T1 agents for magnetic resonance imaging. Moreover, the products were found to capable of catalyzing the oxidation of peroxidase substrate TMB with H2O2, suggesting the peroxidase-like activity of the NaGd(SO4)2:Tb nanorods. The NaGd(SO4)2:Tb was low toxic, a desirable cell viability of ～80% was obtained even at high concentration of -1.25 mg/mL. The NaGd(SO4)2:Tb exposed to H2O2 could generate OH that kill HeLa cells, the results showed that the cell viability of～65% was obtained when NaGd(SO4)2:Tb nanorods of the concentrations of 312.5 μg/mL when incubated with H2O2. Equivalent NaGd(SO4)2:Tb nanorods and H2O2 was incubated with HeLa cells separately, and the cell viability of 98% and 92% were obtained, the results provided a promising way for the study of tumor theranostics. Together with enhanced fluorescent characteristics, the prepared NaGd(SO4)2:Tb could be used as peroxidase mimic and bimodal magnetic-fluorescent imaging agent, which show potential applications in the field of biocatalyst, bioimging and tumor theranostics.