Study On The Preparation Of Stimuli-Responsive Mesoporous Silica Nanoparticles And Application For Controlled Release

In recent years, with the rapid development of nanotechnology,functionalized nanomaterials based on the nano-preparation technology havebeen more and more widely used for the exploration of novel drug carriers. Asan ideal nano-container, mesoporous silica nanoparticles （MSN） have beeninvestigated for the application in novel drug delivery systems, because oftheir large surface area, high pore volume, tunable pore sizes, and excellentbiocompatibility and stability. Especially, the development of MSN-basedresponsive controlled release system that can respond to various stimuli isvery important to improve drug efficacy and reduce drug side effects. In thisthesis, focusing on the construction of novel responsive drug nanocarriers, wedesigned several stimuli-responsive mesoporous silica nanoparticles andinvestigated their preparation and contolled release properties, including thefollowing aspects:1. pH-responsive controlled release system using mesoporous silicananoparticles capped with Poly （Acrylic Acid）.A pH-responsive controlled-release system prepared by electrostaticinteraction between positively charged mesoporous silica nanoparticles andnegatively charged poly （acrylic acid）（PAA） has been developed. PAA’ssolubility and molecular structure is very sensitive to pH. The physical andchemical properties of the as-synthesized MSN were characterized bytransmission electron microscopy （TEM）, X-ray diffraction assay （XRD）,Fourier transform infrared spectroscopy （FTIR）, Brunauer–Emmett–Teller（BET）, and Barrett–Joyner–Halenda （BJH） analyses. Loading amount and pH-responsive release behavior of the system were investigated by using[Ru（bipy）3]Cl2dyes as guest molecules. It was demonstrated that the PAA-capped MSN system was very sensitive to pH and exhibited good property ofpH-responsive release. At neutral pH, positively charged MSN interacted withnegatively charged PAA by electrostatic adsorption, resulting in the closing ofthe mesopores. The guest molecules almost could hardly be released from thepores of MSN. When the pH value was decreased, the percentage release ofdye molecules increased. The guest molecules were released sharply when the pH was less than5. Cumulative release of the dye reached to98%at pH1.0at280min. These results demonstrated that the release of the gust moleculescould be controlled by pH adjustment. This new type of pH-responsivecontrolled release system based on PAA-capped MSN has the advantages ofsimply synthesis, low cost, and large load capacity, which made it havepotential application in drug controlled release.2. Silver ion-responsive controlled release system using mesoporous silicananoparticles capped with G-quadruplex DNA.A silver ion-responsive controlled release system prepared by grafting G-quadruplex DNA as a cap onto the external surface of MSN through a covalentcross-linking method has been developed. The physical and chemicalproperties of the as-synthesized MSN were characterized by TEM, XRD, FTIR,BET and BJH analyses. Loading amount and siliver ion-responsive releasebehavior of the system were investigated by using [Ru（bipy）₃]Cl₂dyes asguest molecules. In the absence of silver ions, G-rich DNA could form aquadruplex structure through π-π stacking between G-G pair mediated bypotassium ions, thus blocking the pore outlets and leading to the entrappedguest molecules hardly released from the pores. When silver ions exsisted, G-quadruplex DNA unfolded into random-coil structure as a result of theinteraction of G bases and silver ions, thus openning the molecular gates andleading to the increased release percentage of dye molecules. Results showedthat the system had a good responsive sensitivity and selectivity to silver ions.When the concentrations of silver ions were0.2mM and0.5mM, thecumulative dye release percentage reached34%and82%, respectively. In thisstudy, we for the first time combine DNA molecule and MSN to develop a newtype of drug controlled release system which is sensitive to silver ions, by useof DNA molecule conformational changes to achieve the purpose of controlledrelease. Therefore, we can adjust the "nano-valve" by adjusting theconcentration of silver ions in the solution, thus achieving the controlledrelease of guest molecules. This carrier is promising for ion-responsive drugcarrier and biosensor.