Study On Applications Of Mesoporous Silica Nanoparticles On Drug Delivery And Biological Detection

Withthedevelopmentofnanobiotechnology,intelligent organic-inorganic composite nanoparticles are causing growing concern.Mesoporous silica nanoparticles?MSN?are very important part of nanomaterials.MSN offer unique characteristics,such as large surface area and volume,tunable pore size,functionalizable surface,and acceptable biological safety and biocompatibility,which are very suitable as the carrier and widely used in the biomedical field.Part OneResearch on Magnetic Drug Transport System Based on Mesoporous Silica MaterialsObjective:To design the amino-functionalized magnetic mesoporous silicon composite materials?AMMS?drug delivery system with preferential targeting behavior and high drug loading capacity,magnetic mesoporous silicon composits materials?MMS?,which are modified by amino group using3-aminopropyl-triethoxy silane?ATPES?,which are used to load anti-cancer drug cisplatin.Methods:A modified solvothermal method was used to prepare Fe₃O₄magnetic nanoparticles.The magnetic particles were characterized by x-ray diffractometer?XRD?,fourier transformation infrared spectrometer?FT-IR?and vibrating sample magnetometer?VSM?,etc.Then,using the magnetic Fe₃O₄ particles and tetraethyl orthosilicate?TEOS?as precursors,the magnetically targeted composite microsphere particles were prepared.The AMMS samples were characterized by scanning electron microscope?SEM?,XRD,FT-IR and VSM.The anti-cancer drug cisplatin was loaded into the AMMS microspheres.The cisplatin concentration was determined using graphite furnace atomic absorption spectrophotometric.Selected encapsulation efficiency of cisplatin as an indicator,orthogonal experiment was designed to screen the optimum conditions of cisplatin loading.The drug release character in vitro was evaluated using dialysis method.Results:The Fe₃O₄ magnetic nanoparticles with particle size of about 10nm were prepared using modified solvothermal method.Then,based on the magnetic particles,AMMS microspheres were prepared.The observation of SEM showed that the AMMS were about 400 nm in diameter.The FT-IR result indicated that the surface of AMMS microspheres was successfully modified by amino groups,which provides the feasibility for subsequent drug loading.The BET specific surface area of AMMS microspheres was 687 m²/g and the pore size was 2⁴ nm.The AMMS were used to load cisplatin.The optimal condition of the orthogonal experiment was as follows:cisplatin concentration of 0.2 mg/mL,incubating temperature of 60°C,incubating time of 9 h.Using the range analysis,the primary and secondary factors were determined in order:time>concentration>temperature.The maximum loading efficiency of cisplatin was 40.36±0.016%.In experiment of drug release in vitro,the CDDP-AMMS microspheres showed an obvious sustained-release character,which fitted the Weibull release rule.The experimental results show that AMMS can be well used for drug loading and has extensive use value in the field of biomedicine.Conclusion:AMMS can be used as an effective drug carrier.Part TwoResearch on the Application of Mesoporous Silicon-Platinum Nanoclusters Complex System in the Determination of H₂O₂ Release from Cancer CellsObjective:To design H₂O₂ bioensors with high activity,good stability and easy operation,expanded mesoporous silicon nanoparticles?EMSN?are prepared and used as a nano-reactors for peroxide-mimicking platinum nano-clusters?Pt NCs?.Methods:Using cetyltrimethyl ammonium bromide as a template,1,3,5-trimethylbenzene as a pore-expanding agent,TEOS as a silicon source,APTES as NH₂ precursor,amino-functionalized EMSNs were prepared.Using EMSN as nano-reactors and bovine serum albumin as the template to synthesis Pt NCs,as a result,EMSN@Pt NCs composites were obtained.The composites were characterized by high resolution transmission electron microscopy?HRTEM?,XRD,FT-IR and fluorescence spectroscopy.Subsequently,thereactionbetweensubstrate3,3',5,5'-Tetramethylbenzidineand H₂O₂ occurred by catalyzing of the EMSN@Pt NCs mimic enzyme.The catalytic activity of mimic enzyme strongly depends on the concentration of H₂O₂.The calibration curve of H₂O₂ was plotted with absorbances?A?as the y-coordinate and concentrations?C?as the abscissa at652 nm.At the end,selecting different cancer cells as model cells and cisplatin,doxorubicin and 5-fluorouracil as stimulators,the catalytic activities of mimic enzyme EMSN@Pt NCs were evaluated through determining the trace concentration of H₂O₂ releasing from the testing cells.Results:EMSN@Pt NCs composite system were successfully synthesized using amino-functionalized EMSN as a nano-reactor.Materials Characterization showed that the diameter of EMSN was about 300 nm.The pore is approximately 9 nm.The diameter of Pt NCs was about 2 nm.The results of enzymatic activity showed that the peroxidase activity of EMSN@Pt NCs was 5 times higher than that of Pt NCs alone.Obviously,as a nanoreactor,EMSN not only greatly enhances the enzyme activity,but also effectively stabilizes the mimic enzyme.The detection of EMSN@Pt NCs was 0.8?M.The bio-detector was applied to detect the trace concentration of H₂O₂released by cancer cells stimulated by different anticancer drugs,which was used to explore the dynamic release of H₂O₂ in living cancer cells.The experimental results show that the biodetector can be used to detect the release of H₂O₂ in cancer cells stimulated by different anticancer drug and explore the dynamic release of H₂O₂ in living cancer cells.Conclusion:The H₂O₂ sensor based on EMSN@Pt NCs peroxidase mimic enzyme has the advantages of high sensitivity,good repeatability and long-term stability.The application of H₂O₂ sensor in determination of trace concentration of H₂O₂ released by living cancer cells under the stimulation of drugs is not just scientific but has application significance in physiological and pathological research field.