Research On The Preparation And Application Of Mesoporous Silica Nano-medicine Carrier

Nowdays,drug chemotherapy is one of the main methods for cancer therapy,but no differential drug delivery can cause very serious side effects.Efficient and safe carriers are of imporatance in drug delivery and controlled release.Mesoporous silica nano-materials have great possibility to be one of the most promising drug carriers because of their unique and excellent physicochemical properties.In this thesis,a series of stimuli-responsive drug delivery systems based on mesoporous silica nanoparticles were prepared by electrostatic self-assembly.In Chapter 1,the classification,properties of mesoporous silica materials as drug carriers are introduced.The recent progress in nano-sized drug delivery systems and targeting drug delivery systems are reviewed,with the emphasis on stimuli-responsive mesoporous silica nano drug delivery systems are introducedIn Chapter 2,a drug delivery system based on MSN capped by alginate was fabricated via electrostatic interaction to investigate its performance of p H-responsive drug release.Mesoporous silica nanoparticles(MSN)were prepared by sol gel method.DOX was loaded into MSN-NH2 which was modified by NH2-group.Alginate modified MSN-DOX(SA@MSN-DOX)was prepared via electrostatic interaction.The alginate acts as a gatekeeper to prevent the loaded DOX from leaking before reaching tumor tissue.The TEM images show that MSN-DOX was successfully coated by alginate.In vitro drug release shows that alginate coating can effectively inhibit the drug release from pore of SA@MSN-DOX at p H 7.4.Through the cell growth inhibition result,it can be seen that cell viability of 293 T cells treated by SA@MSN-DOX is obviously higher than that of MSN-DOX,and there is no significant difference in He La cells,indicated that when alginate wrapping falls off in the low p H environment of tumor cells,the p H-responsive drug delivery system is activated,thus inducing chemotherapy.In Chapter 3,to improve the drug delivery efficiency,a cationic cell-penetrating peptide,protamine sulfate,was introduced to the surface of SA@MSN/DOX nanoparticles to form PS/SA@MSN/DOX nanoparticles.The zeta potential result shows that protamine sulfate was successfully introduced to the surface of SA@MSN/DOX nanoparticles.In vitro drug release shows that protamine sulfate coating can effectively inhibit the drug release from pore of PS/SA@MSN-DOX at p H 7.4.Through the cell growth inhibition result,PS/SA@MSN/DOX nanoparticles exhibited a decreased cell viability of He La cells compared to SA@MSN/DOX nanoparticles indicated that due to the existence of protamine sulfate,the drug delivery efficiencies of PS/SA@MSN/DOX nanoparticles could be significantly enhanced in He La cells.In Chapter 4,to obtain magnetic field and near infrared light dual stimulus responsively drug delivery systems,the graphene oxide and the aminated aptamer were successively assembled onto the surface of the magnetic mesoporous silica nanoparticles(Apt@GO@M-MSNs/DOX).TEM and BET result shows that GO was successfully introduced to the surface of M-MSNs/DOX nanoparticles to form GO@M-MSNs/DOX nanoparticles which has good dispersibility and high specific surface area.In vitro drug release shows that with NIR irradiation,the drug release efficiencies of Apt@GO@M-MSNs/DOX nanoparticles could be significantly enhanced.Through the cell growth inhibition result,due to the existence of magnetic field and NIR irradiation,Apt@GO@M-MSNs/DOX nanoparticles exhibited better cell growth inhibition effect.