Preparation Of Nanocarrier By Using Mesoporous Silica And Selenium To Achieve Synergistic Effect For Cancer Therapy

In recent years,the potential applications of environmental responsive materials in the field of drug delivery have attracted the attention of many scholars.The photothermal response,the reduction response,the pH response and the magnetic responsive materials areespeciallyfavoredbythescholars.Wedesignadrugcarrierwith stimulation-responsiveness through the use of magnetic materials by using the difference of microenvironment between tumor cells and normal cells,such as the difference in concentration of pH and reducing substances,to achieve the active targeting location under the action of external magnetic field.Therefore,the materials of reductive response,pH response and magnetic response have good prospects for application.In this work,we design a kind of nanoparticles with photothermal response based on mesoporous silica.Control the hydrolysis rate and reaction time of tetraethyl orthosilicate in alkaline conditions,obtain the silica nanoparticles of uniform size between 30 nm and50 nm.Preparation of mesoporous shell with St?ber method by using CTAC or CTAB as the template,prepared 3±1 nm the pore size distribution of mesoporous silica dSiO₂@MSN.The suitable and evenly distributed mesoporous mesopore provides a larger specific surface area,which provides good physical conditions for the drug loading.Mesoporous silica nanoparticles contain large amounts of hydroxyl groups on the surface and mesopores,which greatly improve the dispersion of particles in water environment,and a large number of hydroxyl groups on the surface of particles provide good physical conditions for its chemical modification.PAH’s long chain molecules and Cu²⁺could form chelate with photothermal response,load the chelate amount of amino and hydroxyl groups on the surface of mesoporous silica to form hydrogen bonds,so when the dSiO₂@MSN@PAH-CuCl₂ particles excited by 808 nm near infrared light（NIR）in tumor tissue,particle temperature rises high temperature particles cause cell death due to protein and enzyme deactivation,so as to achieve the purpose of photothermal therapy.In addition,on the basis of last work,to fully tap the characteristics of core-shell materials,the nano-selenium particles prepared by the oxidation-reduction reaction of VC and Na₂SeO₃.then prepared Fe₃O₄ nanoparticles by using coprecipitation method,and using sodium citrate modified nanoparticles prepared carboxylated Fe₃O₄ nanoparticles with negative charge（Fe₃O₄-COOH）,and positively charged selenium nanoparticles through electrostatic interactions together with Se/Fe₃O₄ complex as the core,through the St?ber method on the surface of coated mesoporous shell structure,prepared with core-shell structure of Se/Fe₃O₄@mSiO₂ nanoparticles that DLS size is 120 nm,the specific surface area of 274.15 m²/g.The drug molecules were loaded on the prepared nanoparticles by two ways:physical embedding and chemical bonding.The particles’drug load content is 87.1%and the drug load efficiency is 2.8%.And the introduction of nano-selenium increased the toxic effect of drugs on tumor cells and achieved synergistic anticancer effect by Adriamycin and nano selenium.Meanwhile,the magnetic synergistic effect was found by external magnetic field adsorption.In summary,photothermal therapy has many advantages,such as high efficacy,short treatment time,low toxicity,strong regional control and little side effects,so as to reduce the toxic and side effects of anticancer drugs on organisms.The prepared Se/Fe₃O₄@mSiO₂ nanoparticles load DOX note only by physical method but also the use of disulfide bond part chemical bonding agents,which can reduce drug leakage during transportation,and then through the combination of the dose reduction with synergy.The introduction of magnetic nanoparticles Fe₃O₄ particles with magnetic targeting,the introduction of nano-selenium makes it with drugs have a synergistic effect,give full play to the role of core-shell structure.We believe that these two functionalized nanoparticles will provide valuable ideas and references for subsequent research.