Study On Template Removal And Target Modification Of Silica Nanospheres

In recent years,researchers have paid close attention to the issues of bone repair and treatment of bone trauma sites in orthopedic diseases.There are considerable limitations in clinical treatment because of the shortcomings of insufficient quantity and high incidence of donor sites with bone autograft and allograft^[1-4].Researchers hope to deal with bone repair from the field of materials.At the same time,precision treatment has higher requirements for nanocarriers for drug.On the one hand,these carriers need to have targeted intelligent release function,on the other hand,they also need to achieve the goal of“diagnosis and treatment integration”.Mesoporous silica nanoparticles?MSNs?are often used as ideal carriers in the field of drug delivery because of their good properties and biocompatibility.At the same time,combined with the unique magnetic properties of magnetic ferroferric oxide nanoparticles,which makes them have more applications in biomedical fields such as magnetic resonance imaging,targeted drug release,and separation of cells and biomolecules.At present,there are few reports that combine the two materials based on the actual needs of orthopedic treatment.This paper will synthesize mesoporous silica nanocarriers of uniform size and core-shell nanocomposites,and then modify them to give them bacterial targeting and bone targeting functions.Connect the nano valve with pH response on the surface of the material to block the pores and achieve precise drug release,so as to solve the problem that the current material is less enriched in the pathological area,large in size,and has toxic and side effects to normal cells.Finally,through research on targeted testing,biocompatibility,cytotoxicity and antimicrobial drug carrier,it is hoped that this material can be applied to orthopedic trauma environment.This paper summarizes the research progress on the preparation methods and biological applications of MSNs and magnetic iron oxide,and the research status of magnetic-silica nanocomposites.The paper first summarizes the preparation methods and research status of MSNs,magnetic nanoparticles and magnetic-silica nanocomposites,and then proposes the significance of the topic of this paper.In the first part,this paper systematically study the removal effect of the template agent CTAB used in the preparation of mesoporous silica and observe the opening degree of the pores on the MSNs during the removal process.The removal of the template can make clean pores exposed,which is conducive to improve the drug loading rate,and mitigate the toxic and side effects caused by the template.In addition,the removal of its shielding on the surface of the material's silicon hydroxyl group makes it convenient for subsequent modification modified.This study combined with various methods of comparative analysis and obtained a simple and efficient template removal system.The second part mainly studies the construction of dual-targeting system and the design of pH-responsive nanocarriers.The oil-water two-phase method was used to synthesize MSNs with a particle size of about 100 nm as the drug delivery carrier.The silane coupling agent3-aminopropyltriethoxysilane?APTES?was introduced to the outer surface of MSNs through condensation reaction to obtain MSN-NH₂ with amino modification.Then,by the method of EDC/NHS coupling,the surface is modified with carboxyl functional groups while modifying polyethylene glycol with bone targeting and bacterial targeting to form an amide bond by condensation with the amino group on the surface of the MSN-NH₂ material,that is,on the surface of the MSNs modifications make it have targeting properties,and detect its cytotoxicity and human compatibility.On the basis of the targeting system,1-methyl-1H-benzimidazole?MBI?is designed to be connected as a pH-responsive controlled release system,and the valve is blocked after being loaded with the antibacterial drug vancomycin?Van?and discuss its optimal loading in the carrier.In the third part of this paper,oleic acid-modified magnetic Fe₃O₄ nanocrystals?about 20 nm?is used as the core,and a layer of dense silica is wrapped on the surface to obtain a core-shell structure nanocomposite material?Fe₃O₄@nSiO₂?.After condensation reaction of the coupling agent APTES on the surface of Fe₃O₄@nSiO₂,Fe₃O₄@nSiO₂-NH₂ with amino modification was obtained.Then use the EDC/NHS coupling method to modify the surface with carboxyl functional groups and modify the bone-targeted and bacterial-targeted polyethylene glycol by condensation with the amino group on the surface of Fe₃O₄@nSiO₂-NH₂ material to form an amide bond.Fe₃O₄@nSiO₂ has surface modification to make it targeted,and to detect its cytotoxicity and human compatibility.On the basis of the targeting system,through the sol-gel coating method mediated by the surfactant CTAB as a template agent,a sandwich structure magnetic mesoporous silica microparticle?Fe₃O₄@nSiO₂@mSiO₂?with a size of about 80 nm was synthesized on the basis of Fe₃O₄@nSiO₂.The dense silica layer in the middle is selectively etched away to prepare the magnetic-MSNs with yolk shell structure.The Fe₃O₄ core inside this structure can be used for MRI and magnetic response to release drugs,and the external cavity and mesoporous structure can be used to load different types of drug molecules,thus can be applied to“diagnosis and treatment integration”.Finally,the full text is summarized and prospected.The results show that the pH-responsive targeted mesoporous silica material and magnetic-silica composite nanoparticles constructed in this paper release antimicrobial drugs for bone trauma environment.The modified materials have uniform morphology,high specific surface area and pore volume,and have good dispersion in aqueous solution,ethanol solution and PBS solution.The results and research of targeting experiments show that the enrichment degree of the materials with modified targeting molecules in the targeting area is significantly higher than that of the control group without modification of the targeting molecules.The results of biological tests show that the material is less cytotoxic and has good biocompatibility.