Application Of Pore Silica Nanoparticles To Glucose Oxidase Loading And Tumor Cell Transport

Protein therapy has become an important method for the treatment of cancer,immune diseases and metabolic disorders.Compared with traditional chemotherapy and gene therapy,protein drugs have unique advantages in cancer treatment,but there are still many problems that need to be solved in practical applications,such as instability in the blood circulation process,enzyme degradation,short half-life,immunogenicity and inability to penetrate cell membranes.The use of nanocarriers can well overcome the protein display,and mesoporous silica nanoparticles have the advantages of large specific surface area and easy surface modification,which have good application prospects in the field of protein carriers.However,the pore size of traditional mesoporous silica nanoparticles is small(2-3nm).Compared with the size of most proteins(7-8nm),it is difficult to efficiently load proteins in the pores.In order to overcome the above problems,a kind of large pore size(8-9nm)silica nanoparticles(LPNs-Zn O)have been synthesized in this thesis which can be used as protein carriers with zinc oxide quantum dots blocked,and performed related characterization and application.The main research contents are as follows:(1)First,ethyl orthosilicate(TEOS)and styrene are co-polymerized to form mixed nanoparticles.The styrene is then removed by calcination to obtain silicas with larger pore sizes(LPNs).The prepared silica nanoparticles with larger pore size(8-9nm)have a huge specific surface area.A chemical reaction is used to graft the potentially positively charged aminopropyl(-CH2CH2CH2NH2)onto the surface of the LPNs hole(LPNs-NH2)to complete the electrical change of the material.Using fetal bovine serum protein as a model molecule,the protein loading capacity,release behavior and cell entry effect of the pore particles were studied.The results of in vitro experiments and endocytosis experiments show that LPNs have good protein loading performance and can efficiently transport proteins to cells.(2)Considering many problems such as early leakage,explosive release and stimulus response during drug transportation,first choose zinc oxide quantum dots(Zn O QDs)to seal the pores.According to the size of the pore size to be blocked,the particle size of the synthesized zinc oxide quantum dots is about 13 nm.The carboxyl group(-COOH)is grafted onto the surface of LPNs through a chemical reaction.The Zn O QDs were grafted onto the surface of LPNs through the carboxyamine reaction to form LPNs-Zn O.The results showed that Zn O QDs were successfully grafted onto the surface of LPNs,and the LPNS channels were blocked.(3)Glucose oxidase(GOD)is used as the target protein,and silica nanoparticles with a larger pore size are used as the carrier.The GOD is loaded in the particle pores,and then the Zn O quantum dots are grafted to the large pore silica particles(LPNs).)On the surface,the pores are blocked to obtain a "pill" loaded with protein.When cocultured with cells,Hela cells swallow the "pill" into the cells,and the Zn O nanoparticles are ablated by the acidic environment in the cells,opening the GOD in the pores and releasing the GOD.GOD exerts biological effects,thereby achieving an inhibitory effect on tumor cells.In vitro experiments show that the protein transport prepared in this article can respond effectively to pH under acidic conditions.Cytotoxicity tests and endocytosis experiments show that LPNs-Zn O can effectively transport functional proteins into tumor cells to achieve tumor suppression effects.The paper has 90 pictures,6 tables,and 112 references.