Research On Ph And Redox Dual Responsive Mesoporous Silica Nanoparticles For Drug Delivery System

The release of drugs in specific lesions can maximize the efficacy of malignant tumors.However,the current treatment methods primarily rely on conventional cytotoxic drugs that have adverse side effects and only limited effectiveness due to the similarity between cancerous and healthy human cells.The ability to kill diseased cells while causing less harm to the normal cells is of great significance.Among them,novel nano materials as a drug delivery system?DDS?could quantitatively and precisely delivery medicines to the target site on time for the maximum efficacy and the minimum side effects.In order to achieve this goal,we had constructed pH and redox dual-stimuli responsive delivery system?ZnO@CMS?based on colloidal mesoporous silica nanoparticles?CMS?for drug delivery has been developed,in which zinc oxide quantum dots?ZnO QDS?as a capping agent with doxorubicin?DOX?as the model drug.In this paper,a highly stable thiol-functionalized mesoporous silica nanoparticles?CMS-SH?were prepared by co-condensation method.The mesoporous silica nanoparticles containing disulfide bond and terminated with carboxyl group?CMS-SS-COOH?was obtained by a compound of Py-SS-NH₂ which can interact with mercapto groups to form complex compound,then further reacted with maleic anhydride.Then amino-modified zinc oxide quantum dots?NH₂-ZnO QDS?were prepared.Finally,a pH and redox dual-stimuli responsive delivery system?ZnO@CMS?based on colloidal mesoporous silicananoparticles?CMS?for drug delivery has been developed,in which NH₂-ZnO QDS was conjugated on the surface of CMS-SS-COOH by an amidation reaction.In view of this,the following results were obtained by studying the morphology,particle size,entrapment efficiency,drug loading,in vitro release,protein adsorption and hemolysis test,cytotoxicity and cell uptake of the drug-loaded ZnO@CMS.CMS-SS-COOH show a regular spherical morphology and have obvious worm-like channels.The size were relatively uniform and the particle size were about70 nm.CMS-SS-COOH and ZnO@CMS are typical IV type mesoporous structure.But the specific surface area,pore volume,and pore size of ZnO@CMS was smaller than that of CMS-SS-COOH which before zinc oxide quantum dots modification due to the encapsulation.At the same time,the worm-like pores of ZnO@CMS can hardly be seen by TEM.And they also have good stability.DOX as the model drug can be effectively encapsulated in the nanoparticles of ZnO@CMS.The drug loading rate and entrapment efficiency are 6.09%and 97.58%,respectively.The ZnO@CMS-DOX was not released in the absence of GSH.At the same time,under physiological conditions,the drug will not be released.As the concentration of glutathione increases and the acidity increases,the cumulative release rate of the drug significantly increases,and the cumulative release rate of the DOX may reach 60%under double-response conditions.The CMS-SH and ZnO@CMS were compared in terms of protein adsorption and blood compatibility.The experimental results showed that ZnO@CMS had better blood compatibility without hemolysis occurs,and almost no adsorption of bovine serum albumin.The cell viability and cellular uptake tests revealed that the ZnO@CMS might achieve the synergistic antitumor effect on cancer cells due to the cytotoxicity of ZnO QDs.In summary,the mesoporous silica nanoparticles drug delivery system with pH and redox dual response is constructed,which is expected to develop into an excellent anticancer drug loading system.