Construction Of Hollow Mesoporous Silica Nanoparticles Targeting Drug Delivery System

The treatment of cancer has been a difficult problem in the medical field.Although the traditional treatment method of the whole-body administration may kill part of tumor cells,it talso brings serious harm to the body.The side effect can be reduced by anti-cancer drug delivery system,which load anti-cancer drug into nanocarriers and release them into tumor area through normal body circulation,improving the efficiency of anti-cancer drug at the same time.Among the carriers,the hollow mesoporous silica nanoparticles?HMSS?have been studied in the biomedical field due to it's high specific surface area,large pore volume,the easily polished surface and the excellent biocompatibility.In this thesis,HMSS drug delivery system is developed by loading DOX and combining G250 antibody by disulfide bond.The concentration of nanoparticles at tumor area is increased due to active targeting,provided by the specific binding between G250 antibody and G250 antigen,which is highly expressed on the surface of tumor cell.Then the drug is released by disulfide bond breaking caused due to the high-concentrated glutathione in tumor area.The main results are shown as bellow:?1?HMSS nanoparticles are successfully synthesized.HMSS is made by Na₂CO₃alkaline etching method using the cationic surface active agent CTAC as the template agent.The characterization result shows that the HMSS have complete cavity structure and good dispensability.It's BET specific surface area is 998.27m²/g,the average pore volume is 1.43cm3/g.?2?The targetd HMSS nanoparticles polished by G250 antibody are made.Connect G250 antibody to the surface of HMSS particles with the disulfide bond.With the assistance of the specific binding between the G250 antibody and the antigen,the targeted effects to the tumor cells are realized.?3?The linear relation between the DOX concentration and the absorbance is determined.The maximum drug load and it?s corresponding encapsulation rate are calculated based on DOX standard curve formula.The result shows that the maximum drug-carring capacity of HMSS nanoparticles is 1001mg/g and the encapsulation efficiency is 77%.?4?The DOX releasing rate through HMSS is analyzed under different pH conditions.The relation between DOX releasing rate and pH is discussed.It is shown that the lower the pH,the faster the releasing rate and the larger the releasing amount.?5?The effects of cell endocytosis with HMSS-S-S-G250@FITC and HMSS-S-S-G250@DOX are observed.Based on the cell nucleus stained by DAPI,the amount of HMSS-S-S-G250@FITC and HMSS-S-S-G250@DOX at different concentrations is analyzed and discussed.The result shows that the amount of particles is positive correlated with the the particle concentration.?6?The cell viability of Hela cells cultured with different HMSS at different concentrations is calculated.Based on the results,the cytotoxicity of HMSS-SH,HMSS-S-S-Py,HMSS-S-S-G250,HMSS-SH@DOX and HMSS-S-S-G250@DOX,HMSS are anylyzed and compared.The result shows that HMSS,HMSS-SH,HMSS-S-S-PyandHMSS-S-S-G250havebetterbiocompatibility,while HMSS-S-S-G250@DOX has the maximum cytotoxicity.