Preparation And Photothermally/controlled Release Properties Of Porous Silica Based Nanotherapeutics

Combination therapy and tumor microenvironment monitoring are important to improve the effectiveness of cancer treatment.The therapeutic effect of conventional single chemotherapy is not ideal.While the chemo-photothermal combination therapy can significantly improve the effectiveness of chemotherapy.Gold and silver nanoparticles have excellent local surface plasmon resonance effect（LSPR）.The introduction of such materials into nanocarriers can realize the combined treatment of photothermal and chemotherapeutic.Meanwhile,Real-time monitoring of the intracellular environment and the carrier locating can also be achieved using surface enhanced Raman scattering（SERS）technology or fluorescence imaging.In addition,the multifunctional silica nano carriers with different morphologies and structures can be designed and prepared by taking advantage of the tunable structure of silica and the ease of functionalization of the surface.Based on the target binding of hyaluronic acid（HA）to the over expressed CD44 receptor in tumor cells,the HA-coated silica nano carriers can achieve the targeting delivery of the loaded drugs in vivo,controlled release and high uptake by cancer cells.To achieve precise and efficient treatment of cancer,this thesis introduces gold and silver nanomaterials into the silica nanocarriers and coats the HA layer on the carrier surface to construct multifunctional nanocarriers.It has realized the application of tumor cell targeting,drug controlled release,combined photothermal-chemotherapy treatment and real-time monitoring of the internal environment of cancer cells.The main research of this paper is as follows.1.Preparation of mesoporous silica coated gold nanostar carrier and application to Raman detection and combined therapyGold nanostars（GNS）were first synthesized by the seed growth method and then coated with mesoporous silica（m Si O₂）to prepare a mesoporous silica-encapsulated gold nanostars（GNS@m Si O₂）nanocarrier.The gold core（GNS）had a branched morphology with a tip-to-tip diameter of 80-120 nm and a core of 40-60 nm.In this system,the GNS were used as not only photothermal agent but also substrate for SERS.After embedding doxorubicin hydrochloride（DOX）within the GNS@m Si O₂ carrier,hyaluronic acid（HA）is encapsulated on the surface of GNS@m Si O₂ to seal the loaded drug.The DOX-GNS@m Si O₂/HA system exhibited good p H/enzyme responsive drug release behavior and photothermal chemotherapeutic effects.2.Preparation of porous silica-loaded silver sulfide quantum dot carriers and application to fluorescence imaging and combined therapySilver sulfide quantum dots（Ag₂S QDs）were prepared in ethylene glycol（EG）solution using 3-mercaptopropionic acid（MPA）and silver nitrate（Ag NO₃）as precursors.Ag₂S QDs had good water dispersion and near infrared（NIR）fluorescence emission properties（827 nm）.Multi-stage porous silica（p Si O₂）nano carriers with small particle size（～30 nm）,large pore channels and high loading capacity（29.3%）were obtained using an oil-water two-phase method.After embedding Ag₂S QDs into the pores of the inner silica layer,a layer of silica was deposited on the surface of the pores to stabilize the Ag₂S QDs in the pores and construct,a silver sulfide quantum dot/porous silica（Ag₂S/p Si O₂）carrier was constructed.after Ag₂S/p Si O₂ was loaded with DOX,HA was grafted to block the loaded drug and give the carrier the ability to target cancer cells.Ag₂S/p Si O₂/HA has p H/glutathione/enzyme drug release properties and good photothermal combination chemotherapeutic effects.3.Preparation of gold-silver/silver sulfide/porous silica composite nanocarriers for combined diagnosis and therapyA composite nanodrug carrier（Ag₂S/p Si O₂/SG/HA）was constructed based on gold-covered silver triangular nanosheets（SG TNS）,silver sulfide quantum dots（Ag₂S QDs）and porous silicon dioxide（p Si O₂）.The SG TNS has good biocompatibility and photothermal conversion properties.The loading rate of doxorubicin hydrochloride（DOX）on Ag₂S/p Si O₂/SG nanocarriers was as high as 25.48%.After DOX loading,hyaluronic acid（HA）layer was coated on the vector surface,and the HA was used to target the highly expressed CD44 receptor in cancer cells,thus achieving the targeting of tumor cells with the nanodrug carrier.SG TNS retains the excellent LSPR of Ag TNS and can be used as a substrate for SERS to enable DOX release monitoring.The drug release behavior and carrier imaging visualization can be achieved using Raman techniques and fluorescence imaging.