Synthesis Of Functional Rare Earth Nanomaterials And Their Applications In Bioimaging

The rare earth luminescent nanomaterials have been used widely as a new generation of probes in bioimaging. However, only a few studies about the metabolism and biodistribution in vivo of rare earth nanomaterials are reported to date, although metabolism and biodistribution play a crucial role for their biological safety assessment. Moreover, the quantitative analysis of the biodistribution of nanomaterials in vivo was mainly limited to the technique of ICP-AES to detect the quantity of the rare earth ions in tissues, which is not intuitive and have tedious steps. In addition, to improve bioimaging penetration depth and resolution, the luminescence quantum efficiency needs to be improved and the excitation and emission wavelengths should be optimized to reduce the absorption and scattering by biological tissue. In this thesis, the following three sections have been carried out:1. Radioactive/upconverting NaLuF4:153Sm3+, Yb3+, Tm3+ nanoparticles for dual-modality UCL and SPECT bioimaging153Sm (Eγ=103 keV), a rare-earth radioisotope, has a physical half-life of 46.3 h and emits medium energy beta particles, making it suitable for long-term single photon emission computed tomography (SPECT) imaging and long-term biodistribution quantification studies. Here, we have synthesized Yb3+, Tm3+ and 153Sm3+ co-doped NaLuF4 nanoparticles using a one-step hydrothermal method. Moreover, these radioactive/upconverting NaLuF4:153Sm3+,Yb3+,Tm3+ nanoparticles have been applied for dual-modality upconversion luminescence (UCL) and SPECT bioimaging in vivo. The biodistribution of the NaLuF4:153Sm,Yb,Tm nanoparticles within living mouse has been quantified using gamma counter. The histological assessment of tissues and serum biochemistry assays indicated that these nanoparticles had no apparent toxicity for 7 days post-injection.2. Nd3+-doped nanoparticles for both near-infrared Ⅰ and Ⅱ luminescence bioimaging in vivoWe have synthesized Nd3+doped nanomaterials which can emit bright luminescence at ～890 nm (NIR Ⅰ window) and ～1060 nm (NIR Ⅱ window) simultaneously. Using NIR Ⅱ luminescence as collected signal and 808 nm laser as excitation, the best in vivo imaging results could be achieved, compared with the other conditions including NIR Ⅰ luminescence imaging under 730 nm excitation, NIR Ⅱ luminescence imaging under 730 nm excitation, and NIR Ⅰ luminescence imaging under 808 nm excitation. Using InGaAs CCD with a high quantum efficiency at 1000-1400 nm as detector, more vessels in the arms, legs and head of the mice could be seen in the NIR Ⅱ luminescence imaging in vivo under 808 nm excitation.3. Long-term in vivo biodistribution and toxicity of Gd(OH)3 nanorodsDue to its seven unpaired electrons, Gd(OH)3 nanorods have been reported to be a good magnetic resonance imaging (MRI) contrast agent. Meanwhile, the rare earth hydroxides can be degraded under the acidic conditions such as exist in the lysosomes. However, no studies concerning long-term toxicity, biodistribution or in vivo sequestration and excretion of these one-dimensional nanorods were reported. Here, we synthesized radioactive Gd(OH)3:153Sm nanorods to investigate the in vivo biodistribution and metabolism of the Gd(OH)3 nanorods by SPECT imaging and gamma-counter measurements. Furthermore, in vivo toxicity studies indicated that mice intravenously injected with up to 100 mg/kg of Gd(OH)3 survived without any evident toxic effects at exposure times as long as 150 days.