Construction And Property Research Of New Drug Delivery Platform Based On Mesoporous Silica

Mesoporous silica?mSiO₂?has been widely applied in medical science especially in drug development,transplantation of artificial organ and synthesis of drug carriers due to its advantages such as alterable channel with nanoscale size,adjustable morphology,large pore volume,high specific surface area,surface easily to be grafted and good biocompatibility.In this thesis,mSiO₂based drug delivery systems were prepared and pH-,and light-responsive drug delivery was investigated.To prepared a novel drug nanocarrier,Fe₃O₄@Au@SiO₂,for targeted and near-infrared irradiation-controlled delivery of Etoposide?VP16?.Nanoparticles of Fe₃O₄,Au and SiO₂ with low toxicity and good biocompatibility are facilely assembled for the construction of a coreshell structure.The mesopores within the SiO₂ shell provide enough space for the encapsulation of VP16;meanwhile,the Fe₃O₄ core with superparamagnetism and the AuNPs interlayer having superb lightthermal conversion ability facilitate targeted and near-infrared irradiationcontrolled VP16 delivery,respectively.In a novel drug nanocarrier,polypyrrole?PPy?/mSiO₂/graphene quantum dots?GQDs?,the PPy core functions as a photothermal agent for the conversion of near-infrared irradiation to heat;meanwhile,the mesopores in the mSiO₂ shell provide Methotrexate?MTX?molecules with a better accommodation.GQDs acting as a gatekeeper are introduced to the outer surface of the drug loaded PPy/mSiO₂ through the formation of H-bonds.Under the irradiation of near-infrared light,the temperature of the nanocarrier is gradually increased due to the excellent light-heat conversion ability of PPy.As a result,the H-bonds between GQDs and mSiO₂ are broken,the GQDs cap is removed from the PPy/mSiO₂/GQDs,and thus near-infrared irradiationcontrolled release of MTX from the nanocarrier is successfully achieved.Tubular mSiO₂?T-mSiO₂?modified with mercapto groups was synthesized using?3-mercaptopropyl?trimethoxysilane as the silicon source,which was then grafted with disulfide bond?SS?via the interactions with dipropyl sulfide.Finally,chitosan?CS?was grafted to the surface of SS-T-mSiO₂ to block the channels of mSiO₂.5-Fluorouracil?5-FU?was loaded within the resultant composites,and then the disulfide bond was broken in the presence of glutathione?GSH?and pH-responsive delivery of 5-FU from the carrier was achieved.