Preparation And Multi-modal Imaging Properties Of PEI Coated Upconversion Gene Carriers

Development of gene carriers with both effectiveness and safety is in the pivot of gene therapy. Recently, several major progresses was made on the fabrication of inorganic nano-materials, the the advantages such as ease of preparation and surface modification and low cytotoxicity make it a great candidate for the gene carriers. Lanthanide-based uponversion nanoparticles (UCNPs) attracted a lot of attention in the biomedical field due to the unique luminescence characteristics. Besides the upconversion properties, Gd-doped and Yb-doped UCNPs show great potential as the MRI/CT contrast agent. However, study on the UCNPs based gene carriers is very scarce. As far as we know,the examples as to UCNPs based gene carriers with multi-modal imaging property have not been reported.In this dissertation, we constructed two gene carriers platform based on NaYF4:Yb/Er and NaGdF4:Yb/Er, respectively. We analyzed the crystal structure, morphology, biocompatibility,in vitro transfection et al. of both the two platforms.The NaYF4: Yb/Er gene carriers were synthesed in a solvent thermal method, the as-prepared nanoparticles show good uniform morphology and can be dispersed in water. The nanocarriers use the PEI coating to absorb DNA molecules. In the experiment of EGFP plasmid transfection, the gene carriers show good transfection efficiency. The up-conversion property enables us to track the location of gene carriers in cells.The NaGdF4:Yb/Er@PEI multifunctional gene carriers were fabricated by a thermal decomposion method,followed by a ligand exchange protocol. The gene carrirs show great biocompatibility in the MTT assay and can be well dispered in water. We found the gene carriers preserve the advanges of PEI polymer while overcome the safety issue. The in vitro EGFP plasmid transfection and bcl-2 gene knock down experiment both demonstrate that this platform is as effective as PEI polymer. Finally, the MRI/CT/UCL tri-modal imaging property was demonstrated in vivo. The gene carriers show great potential as a contrast agent in MRI and CT. Besides, the gene carriers also exhibit good skin penetration ability in mice.