Preparation Of Responsive Degradable Silica Nanospheres And Their Drug Controlled Release Performance

With the rapid development of material chemistry and nanomedicine,nanosized drug carriers have become one of the important development directions of nanobiomedical field,bringing revolutionary changes to the treatment of malignant tumors.By loading the drug in the nanocarriers,the drug can be released at a fixed point under control.Among them,mesoporous silica has been proved to be a valuable drug delivery platform for its excellent physical and chemical properties.In order to maximize the biomedical applicability of mesoporous silica-based drug carriers,it is important to ensure their ideal controlled release property and biodegradability under physiological conditions.In this paper,the biodegradable mesoporous silica nanocarriers were prepared by in-situ doping of metal elements or S-S structural units.Biocompatible polymer as the gating switch was constructed on the surface of the doped carriers to block the loaded drugs,combining CuS nanoparticles,the drug delivery system would display the controlled release,monitoring and degradation of the carrier.The main research content includes the following four parts.?1?Preparation of Mn-doped mesoporous silica nanospheres and their pH/GSH responsive releaseMn doped mesoporous silica nanospheres were prepared by in-situ doping method,with particle diameter of 90?100 nm and pore diameter of 3?5 nm.Based on the dissolution characteristics of Mn ions under acid/reduction conditions,the nanospheres can be degraded in response to acid/reduction.Doxorubicin was used as the model drug to load,and pH-responsive polydopamine?PDA?was selected asthe gated switch to block the drug.Experiments results indicates n that the Mn-doped silica carrier can be completely degraded within 48 h in the presence of GSH and acidic pH condition.The drug delivery system exhibits a good pH-responsive drug release.The cytotoxicity test shows that the carrier and its degradation products have good biocompatibility,and the drug delivery system has enhanced cytotoxicity.?2?Preparation of S-S doped mesoporous silica nanospheres and their pH/GSH responsive releaseS-S doped dendritic mesoporous silica nanospheres were prepared by in-situ doping.Towards the acidic pH and high level GSH of tumor microenvironment,using the doped mesoporous silica as carrier,doxorubicin as the model drug,the pH/GSH responsive drug release system was designed and constructed by coating DAD/Cys as the gated switch to block drugs.Because there exists the pH-sensitive Schiff base?C=N?bond between the DAD/Cys coating layer and the surface of the carrier,the carrier has the property of emitting blue fluorescence,which can monitor the drug release process according to the change of fluorescence signal in the drug release process.The results show that the drug delivery system exhibits good responsive release behavior in the releasing media containing GSH and acidic pH.And the change of fluorescence intensity of the carrier is negatively correlated with the released amount of drug during the release process.The doped carrier displays good GSH/pH-responsive degradation behavior.The cytotoxicity test shows that the carrier and its degradation products had good biocompatibility.?3?Preparation,photothermal treatment and NIR/GSH responsive release of degradable CuS@SiO₂ nanospheresThe composite nanosphere was prepared with CuS nanoparticle as the core,and S-S dopeddendritic silica as shell.The S-S doped silica carrier has good photothermal stability,photothermal transformation ability and good GSH responsive degradation performance.After the doxorubicin model drug was loaded,carboxymethyl-?-cyclodextrin was used to block the drug-carrying channels,and a controlled-release system of S-S doped silica with photothermal characteristics was constructed.The drug delivery system shows good response to GSH and near-infrared light.Cytotoxicity experiments show that the carrier and its degradation products have good biocompatibility,and the carrier-mediated drugs have enhanced lethality against Hela cells.?4?Preparation,photothermal treatment and triple-response release of auto-fluorescent degradable CuS@SiO₂ nanospheresThe pH/GSH/NIR-responsive drug release system was designed and fabricated,using S-S-doped mesoporous silica with CuS nano-core as the carrier and chitosan/curcumin as gate keeper.Chitosan was firstly coated on the carrier surface,and then curcumin with green fluorescent property was modified on the carrier surface by forming Schiff base bond with chitosan.The results showed that the drug delivery system exhibits good response release to pH,GSH and NIR.During the drug release process,the change of fluorescence intensity of the carrier is opposite to the cumulative drug release rate,which can be used to monitor the drug release.The carrier showed good GSH concentration-dependent degradation behavior.Cytotoxicity experiments showed that the carrier and its degradation products have good biocompatibility.