Synthesis Of Functional Nanoparticles For The Assembly Of Nano-sized Drug Carrier

Due to their unique physicochemical properties,nanomaterials have been widely applied in the field of catalysis,material,energy,environmental protection,biomedicine and so on.The synthesis of biocompatible nanomaterial with unique properties and the application of these nanomaterials for early diagnosis and therapy of cancer are the main content for nanomedicine and have received more and more attentions recently.Achieving controlled synthesis of nanomaterials with desired morphology,property and surface functionality is of significant important for biomedicine,especially for drug delivery.Aimed at the practical applications of nanoparticles in cancer therapy,this dissertation focuses on the design and preparation of nano-sized drug carrier.In this dissertation several nanoparticles were synthesized and assembled into multifunctional nanocomposites as drug carrier for the controlled drug release and cancer therapy.The main research results are summarized briefly as follows:(1)PEGylated gold nanoparticles were prepared with a typical ligand exchange reaction.The optical properties and stability of these Au NPs in water,organic solvent and in the film form were systematically investigated.The SPR of Au NPs was found to be greatly influenced by PEG length and coverage density in the film form.PEGylated Au NPs exhibits high stability in water even they were aggregated.Nevertheless,they will gradually grow into large particles in chloroform and after dried into a film when poorly PEGylated.UV-vis and electron microscopy were used to monitor this evolution process.Three distinguishable stages(the assembly,fusion and growth of gold nanoparticles)were observed.Direct observation of the intermediate state also confirms the growth mechanism of original gold nanoparticles is through collision and fusion of entire nanoparticles rather than Ostwald ripening.(2)A silica gel-based liquid chromatography method was developed to analyze and to separate polyethylene glycol coated gold nanoparticles according to both their core size and surface functionalization.Via column chromatography,we found that as prepared PEGyalted Au NPs were separated into two fractions on the column.The trapped portion was considered to have significant residual DDA on the gold surface.Remarkably,the chromatographic method showed its abilities to separate well ligand-coated and monodispersed gold nanoparticles as confirmed by dynamic light scattering(DLS).In addition,core size separation was achieved via this simple column chromatography process.Consequently,this simple column chromatography method provides a good opportunity to further tailor nanoparticles after initial synthesis and allow more precise control over the size and surface functionality on nanoparticles.(3)A facile one-pot method was presented for the preparation of colloidal stable,monodispersed,highly PEGylated CuS@mSiO2-PEG nanocomposites in sub-50 nm size.The as-prepared material exhibited good photothermal efficacy and pH-responsive drug release behavior,which makes it excellent vehicle for the combination of photothermal and chemotherapy.Since mSiO2-based nanocomposites are heavily explored recently,this synthetic method may provide a standard approach for the preparation of colloidal stable,highly PEGylated mesoporous silica nanocomposites for biomedical applications.(4)With rational design,high quality 795 nm excited upconversion nanoparticles with core-shell-shell structure with successfully prepared.The Nd doping in the first shell layer enabled their ability to absorb 795 nm laser and the energy finally transferred to Er ions in the core to emit green light around 543 nm.We systematically optimized the doping amount of Nd and Yb in order to achieve high emitting efficiency.After coated with amino group and PEG modified mesoporous silica,these nanoparticles were conjugated with a photodynamic therapy drug Rose Bengal.The generation of singlet oxygen under 795 nm laser irradiation was confirmed with the decay of DPBF,which could be useful for the photodynamic therapy of cancer operated with a tissue-penetrable NIR laser.(5)We described a modular approach to prepare multi-functional hollow mesoporous silica nanocapsules with encapsulated IONPs.The hollow mesoporous silica nanostructures provide a large drug loading capacity and sustained release property,while the loaded IONPs can serve as magnetic field responsive hyperthermia agents.Moreover,the magnetic field response of the synthesized nanocapsules can significantly promote the release of payload to the surrounding media.The synthesized hybrid nanocapsules provide a promising platform for the combination of hyperthermia and chemotherapy for cancer treatment applications.