Construction And Biological Application Of Novel Hyaluronic Acid Supramolecular Nanoparticles

Cancer is a major problem in human medicine with the morbidity and mortality rapidly increasing with the years.Early detection and treatment of cancer cells is an effective way to improve the survival rate of cancer patients.But so far,there are still many challenges in distinguishing between cancer cells and normal cells at the cellular level and specially killing cancer cells while leaving healthy cells intact.Therefore,the construction of targeted and release controllable drug/gene supermolecule delivery systems became research focus in anti-cancer studies in recent years,and it is still a difficult point to simplify the drug/gene supermolecule delivery systems without redusing their bioactivities.In the work of this paper,A series of targeted drug/gene delivery nanoparticles based on hyaluronic acid through cyclodextrin and MOF as module were designed to realize linkage and controllable release toward plasmid-DNA and targeted fluorescence imaging toward cancer cells.The main contents of the thesis are as follows:1?A double positive charged guest bearing one adamantyl group on one side and two quaternary ammonium chains on the other side and ?-cyclodextrin modified hyaluronic acid were synthesized.When mixed in the aqueous solution,supramolecular nanoparticles with negative charged HA shell and positive charged quaternary ammonium chains core was fabricated through the supramolecular interaction between adamantane and?-cyclodextrin.This nanoparticle could bond plasmid-DNA effectively,and when the ester group on the quaternary ammonium chain was hydrolyzed to form zwitterionic group,the controllable plasmid-DNA release would be realized.2?Adamantane modified tetraphenylethylene was synthesized,when the molecule was mixed with ?-cyclodextrin modified hyaluronic acid,a supramolecular nanoparticle with hydrophilic HA shell and hydrophobic tetraphenylethylene core was fabricated through the supramolecular interaction between adamantane and ?-cyclodextrin.Aggregation-induced emission occurred in the tetraphenylethylene core,which could realize targeted fluorescence imaging toward cancer cells.3 ? The phosphorous acid modified hyaluronic acid and the porous nano-structural Prussian blue MOF were synthesized.When mixed in the aqueous solution,Prussian blue nanoparticles coated with biotropic hyaluronic acid were obtained through strong bonding between phosphorous acid groups and iron ions on the surface of PB MOF,the porous structure of which was used to load with the anticancer drug to construct organic-inorganic hybrid nanoparticles targeting drug delivery.