Preparation Of Mesoporous SiO₂-based Janus Nanocomposites And Research Of Microwave Controlled Drug Release

Drug delivery systems based on nanomaterials have been widely applied in targeted cancer therapy.Nanomaterials are generally classified into organic nanomaterials and inorganic nanomaterials,in terms of drug transportation,inorganic nanomaterials have better biocompatibility and easier modification compared with organic nanomaterials.Multi-component“core-shell”nanoparticles in inorganic nanomaterials have multifunctional properties,therefore,“core-shell”nanocomposites have potential application in drug delivery,biomedical imaging and therapy fields.Normally,“core-shell”nanomaterials are made up of two or more substances,forming a single or multilayer structure,the interlayer covering results in interference between different components,which weakens the functional properties of the nanomaterials.However,biplanar/polyhedral Janus nanomaterials are able to perform their respective characteristics and key roles.Hence,Janus-type nanomaterials have been widely explored and applied to catalysis,sensing,optical imaging and drug delivery fields.In order to achieve targeted delivery,efficient loading and microwave-controlled release of anticancer drugs,According to the functional characteristics of the materials,we designed elaborately and synthesized Janus nanomaterials based on spatial structure.The heterostructure nanomaterials compared possessing microwave absorption and drug loading functions,which inhibiting the interlayer covering of the traditional“core-shell”structure so as to avoid the shielding and interference between compositions.Several mesoporous silica(mSiO₂)-based nanocarriers with special morphology and microwave absorption function were synthesized for the first time in the work.Firstly,the magnetic dielectric loss-absorbing material Fe₃O₄nanocarrier was introduced into the study of microwave-controlled drug release to construct Janus-type Fe₃O₄&mSiO₂nanoparticles.The microwave-thermal conversion performance of Janus nanoparticles was different from those of the“core-shell”structure Fe₃O₄@mSiO₂.Secondly,the reaction conditions,mechanism and microwave-thermal conversion mechanism of heterogeneous configuration from black titanium dioxide(TiO_2-x)and mSiO₂were explored in detail.Subsequently,in order to further improve the microwave-thermal conversion performance of the nanocarriers,magnetic dielectric loss type material(Fe₃O₄)and dielectric loss type material(TiO_2-x/ZnO)were combined by surface modification.Finally,to avoid the problem that the surface modification occupied the carrier pore,leading to the reduction of drug loading rate,we purposely designed the microwave absorption functional material as a“core-shell”structure,then combined with mSiO₂in the opposite direction.Thus,the microwave absorbing materials and drug-carrying mesoporous materials could be separated to a certain extent and combined relatively uniformly so as to realize the multifunctional characteristics of nanocarriers.Based on the above design idea,the work mainly is carried out the following four parts of researches,the specific research content and main research results are as follows:(1)Magnetic Janus Fe₃O₄&mSiO₂with heterostructure was prepared by hydrothermal method and sol-gel method as a nano-carrier loading anti-cancer drug(DOX),Janus Fe₃O₄&mSiO₂nanocarriers were applied to microwave absorption and controlled-release of drugs.The results indicated that the performance of Janus Fe₃O₄&mSiO₂nanocarriers in microwave-thermal transformation is significantly better than that of“core-shell”structure Fe₃O₄@mSiO₂nanocarriers.Meanwhile,the cumulative drug loading rate of Janus Fe₃O₄&mSiO₂carrier after 24 h reached 36.40 wt%.The loading process of DOX was exothermic and the interaction between DOX and Janus Fe₃O₄&mSiO₂carrier was mainly van der Waals force,and the coupling of DOX and carrier created electrostatic interaction.The rate of drug release was remarkably increased from 42.61 wt%to 89.05 wt%after microwave stimulation at p H 7.0.In addition,the effect of Janus Fe₃O₄&mSiO₂-DOX on the activity of He La cells was investigated by MTT assay.The findings showed that Janus Fe₃O₄&mSiO₂-DOX could promote the apoptosis of He La cells.(2)Magnetic loss and electrical loss are two kinds of microwave absorption mechanism,in the second chapter of the work,magnetic loss Fe₃O₄nanospheres have been selected as microwave absorbent,therefore,electrical loss TiO_2-xnanospheres with surface defects were used as microwave absorbent in this chapter to construct Janus TiO_2-x&mSiO₂nanocarriers for the first time.Janus TiO_2-x&mSiO₂nanocarriers were formed by growing rod-like mesoporous silica onto TiO_2-xsurface,the specific surface area and cumulative drug load of the whole carrier were 203.25 m²/g and 38.00 wt%,respectively.The non-covalent interaction between DOX and Janus TiO_2-x&mSiO₂carrier is mainly van der Waals force,and the loading of DOX was an exothermic process.At 360 min and p H=7.0,5.0 and 3.0,drug release rates were61.03 wt%,69.17 wt%and 89.24 wt%,respectively.The rate of drug release was significantly promoted from 61.03 wt%to 88.01 wt%after microwave stimulation at p H=7.0.Thus,the Janus TiO_2-x&mSiO₂multifunctional carrier can not only release the drug under the control of p H but also be further triggered by microwave stimulation.(3)In order to further improve the microwave-thermal conversion performance of the carrier,the dielectric loss type material and magnetic loss type material were integrated to generate multi-component species.In this chapter,the magnetic dielectric loss-type Fe₃O₄featuring small size was firstly introduced into the surface of TiO_2-x&mSiO₂nanocarrier through surface modification.When DOX was loaded,dielectric loss zinc oxide(ZnO)was used to seal the pores,and a novel“multiped”TiO_2-x&mSiO₂-Fe₃O₄-DOX-ZnO nanocarrier was finally obtained in a controllable manner.The carrier has the multifunction features including microwave absorption,magnetic targeting and“gating”of drug release and so on.Moreover,it was found that“multiped”TiO_2-x&mSiO₂nanocarriers could be constructed from TiO_2-xnanospheres with different particle sizes.The cumulative drug loading rate of“multiped”TiO_2-x&mSiO₂-Fe₃O₄-DOX-ZnO nanocarrier increased to 50.70 wt%after 270 min,compared with the drug loading rate in chapter 3,the nanomaterials in this chapter show higher drug loading performance.At 210 min and p H=7.0,5.0 and 3.0,the drug release rates were 70.28wt%,75.17 wt%and 87.41 wt%,respectively.The experimental results indicated that the drug release behavior was p H-dependent,and the drug release rate reached 82.16 wt%after microwave stimulation and p H=7.0.In addition,“multiped”TiO_2-x&mSiO₂-Fe₃O₄-DOX-ZnO nanomaterials can also accelerate the apoptosis of He La cells.(4)In chapter 4,the introduction of small size Fe₃O₄and ZnO occupied parts of the pores of mSiO₂,which leading to the reduction of drug load rate in theory,therefore,the functional end of microwave absorption materials was ingeniously designed as Fe₃O₄@n SiO₂@TiO_2-xnanospheres featuring“core-shell”structure,the“biped”Fe₃O₄@n SiO₂@TiO_2-x&mSiO₂nanocarrier was constructed for the first time by growing mSiO₂onto its surface by sol-gel method.The specific surface area of the carrier was 222.8 m²/g,the saturation magnetization was 12.98 emu/g,and the carrier also had a good microwave-thermal conversion performance.Meanwhile,the cumulative drug loading rate of“biped”Fe₃O₄@n SiO₂@TiO_2-x&mSiO₂nanomaterials increased to 40.07 wt%after 240 min,and the rate of drug release was significantly increased from 21.21 wt%to 84.73 wt%after microwave stimulation at p H=5.0.The results indicated that the“biped”Fe₃O₄@n SiO₂@TiO_2-x&mSiO₂nanocarrier triggered by dual stimulus including p H and microwave is expected to be further applied in drug delivery system.