Magnetic Colloidal Nanocrystal Assembly, Functionalization, And Application As Drug Delivery Vehicle

With the rapid development of nanobiotechnology, multifunctional nanomaterials as drug vehicles have been intensively pursued for their technological and fundamental scientific importance. Particularly in the field of targeted therapy, multifunctional magnetic microspheres as targeted drug delivery carriers can realize targeted and quantitative release of drugs and endow them with great potential application in biomedical field. Based on the foregoing reasons, the research interest of this thesis is focused on the preparation of strong magnetic responsive composite microspheres and their application as drug delivery vehicles. The main conclusions in this thesis are listed as following areas:1) By controlling the assembly process of the primary magnetic colloidal nanocrystal and consequently manipulating the secondary structures through solvothermal synthesis, efficient and facile routes for the fabrication of solid, hollow porous, mesoporous magnetic colloidal nanocrystal clusters were developed. In the fabrication of solid magnetic colloidal nanocrystal clusters, the size of clusters could be easily turned from～90 to～260 nm by simple change of the reaction time. In the fabrication of hollow porous magnetic colloidal nanocrystal clusters, the morphology transformation of spherical clusters from solid to hollow to hollow porous shells could be controlled in a straightforward fashion through the reaction time. In the fabrication of mesoporous magnetic colloidal nanocrystal clusters, the specific surface area of clusters could be controlled from 27 to 134 m2/g, pore volume from 0.11 to 0.57 cm3/g, and mean pore diameter from 4.7 to 6.2 nm by change of the feeding amount of PGA. Magnetic characterization showed that solid, hollow porous, mesoporous magnetic colloidal nanocrystal clusters all have high saturation magnetization. 2) The solid magnetic colloidal nanocrystal clusters as model unit were coated with a silica layer through a sol-gel process and core-shell Fe3O4/SiO2 composite microspheres were obtained. The thickness of SiO2 shell could be controlled from～10 to～84 nm in a straightforward fashion of feeding amount of silica source (TEOS). Then, MPS was used as a silane coupling agent to modify the surface of silica-coated magnetic colloidal nanocrystal clusters, which led to the formation of terminal C=C bonds on the surface of the cores. Finally, a robust polymer coating on the core surface by copolymerization of anchored MPS with NIPAM (monomer) and MBA (cross-linker) was formed via seed precipitation polymerization, resulting in monodisperse high magnetization core-shell Fe3O4/SiO2/PNIPAM magnetic thermosensitivity composite microspheres. The temperature sensitivity could be controlled by changing the cross-linking density.3) The hollow porous and mesoporous magnetic colloidal nanocrystal clusters as model units were used as drug delivery vehicles for paclitaxel (TXL), a hydrophobic anticancer agent. TXL was incorporated into clusters using the nanoprecipitaion method. The drug loading content of hollow porous and mesoporous magnetic colloidal nanocrystal clusters can reach 20.2 wt.% and 35.0 wt.%, respectively. The antitumor efficacy of the drug-loaded hollow porous and mesoporous magnetic colloidal nanocrystal clusters measured by MTT assay was clearly enhanced, compared with free drugs. It is worth noticing that the performance of antitumor efficacy of mesoporous magnetic colloidal nanocrystal clusters much better than hollow porous magnetic colloidal nanocrystal clusters.