Study On The Synthesis Of Upconversion Nanoparticles And Their Application In Photodynamic Therapy And Detection Of Biomolecules

In recent years, a growing number of new nanomaterials have been regarded as the research focus due to their unique optical properties, a variety of biosensors have been constructed based on new-emerging nanomaterials. Upconversion luminescent nanomaterials, which can convert near infrared light into visible light through a multi-photon mechanism, with low energy light, low background, high and stable luminous intensity, emission wavelength can be adjusted by controlling the composition and so on, this advantages make it has been widely used in biology detection, its good bio compatibility, high tissue penetration ability and low toxicity allowed it to get a strong development in cells, tumor imaging diagnosis and therapy. Based on this, the three parts of paper about upconversion nanoparticles are as follows:1. Oil-soluble NaGdF4:Yb,Tm/NaGdF4and NaYF4:Yb,Er nanoparticles were obtained by solvothermal method. The results showed that compared to the NaGdF4:Yb,Tm/NaGdF4(main emission peak at475nm), NaYF4:Yb,Er (main emission peak at540nm and650nm) have larger particle size and higher luminous efficiency. On this basis, we selective NaYF4:Yb,Er for further surface modification to improve the dispersibility of UCNPs. To obtain the hydrophilic UCNPs, we further functionalized the nanoparticles through the silica shell coating (stober method) and the phospholipids shell coating. Results showed that phospholipids coated UCNPs are more dispersive and more thin than silica coated UCNPs and phospholipids coated UCNPs hardly affects the intensity of emission light, which laid the foundation for further application.2. Based on the optical properties of UCNPs and the highly specific recognization ability of aptamer, we developed a simple identification and photodynamic therapy of tumor cells. The principle was as follows:the phospholipid coated UCNPs can assembly zinc phthalocyanine in the hydrophobic layer by hydrophobic interaction, which is capable of efficiently absorbing UCNPs’s light at650nm and released singlet oxygen to induce cells apoptosis. We further crosslink the mercapto group of phospholipid with the AS1411aptamer which capable of specific recognition of tumor cell surface high expression of nucleolin and then harrow to photodynamic therapy of tumor cells. Results showed that the sensor can be a good rake to the human breast cancer cell and kill human breast cancer cells by photodynamic therapy, while almost no influence on normal human breast cells in vitro.3. Based on the optical properties of UCNPs and the special electronic properties of graphene oxide, we developed a simple, highly sensitive method for anti-HIV-1gp120detection. The principle of the upconversion FRET-based biosensor was as follows:the polypeptide from HIV type1glycoprotein gp120was first conjugated with the phospholipid to form phospholipid-peptide conjugates, which, as well as PEGylated phospholipids, were then used to prepare the peptide functionalized UCNPs through a one-step assembly driven by the hydrophobic van der Waals interactions between the hydrophobic tail of the phospholipids and the primary oleate ligands on the UCNP surface. When adding GO, peptide-functionalized UCNPs could adsorb on the surface of GO via π-π stacking interactions and hydrophobic interactions and the upconversion fluorescence could be completely quenched through energy transfer or electron-transfer processes. In contrast, in the presence of the antibody, the peptides preferred to bind to their antibody, leading to the formation of peptide-antibody complexes. Therefore the interactions between the peptides and GO would be inhibited, which would keep the UCNPs far away from the GO surface, resulting in a decrease in quenching efficiency and the recovery of upconversion fluorescence. The results showed that the sensor can be used for antibody sensing both in an aqueous buffer and in a serum matrix with comparable performances, under the optimal conditions, the upconversion fluorescence intensity increased with the increasing antibody concentration, and the relative fluorescence intensity was linearly related to the antibody concentration in the range from5nM to150nM. The detection limit of antibody in an aqueous buffer was calculated to be2nM. In addition, the recovery experiment was also performed. Four human serum samples spiked with different concentrations of anti-HIV1gp120antibody were determined, and the results showed the recoveries were from95%to108%with RSD around6%, which are acceptable for quantitative assays performed in biological samples.