Preparation And Drug Delivery Application Of SiO₂-Based Mesoporous Luminescent/Magnetic Composites

Among all kinds of porous materials, ordered mesoporous silica materials are of greatinterest due to their unique features such as high surface area, large pore volume, goodbiocompatibility, ordered mesoporous structure, tunable pore size, and well-defined surfaceproperties for modification, which provide them enormous potential in the fields of laser,biomedicine, catalysis, sensing and environmental technology, especially in biomedicine,including drug delivery, bioimaging, photothermal therapy and photodynamic therapy.However, along with the development of pharmacology, pathology and therapy method, therequirement of structure, function, size and composite for materials is urgent. And the singlefunction of pure mesoporous silica materials can not satisfy the needs already. So, functionalmesoporous silica materials come into being, and studied widely. Herein, we designed severalluminescent and/or magnetic mesoporous silica composites with different combination andstructures, and investigated their favorable drug release properties. In these composites, ironoxide with good biocompatibility, simple synthesis method and strong magnetism was choseas magnetic material. And rare earth phosphors with high chemistry/photochemistry stability,narrow emission bandwidths, low toxicity, large Stokes shifts, long fluorescence lifetimes,and low photobleaching were picked as luminescent materials.Luminescent and/or magnetic mesoporous silica composites possess different structures,including embedded structure and core-shell structure. The embedded structure meansembedding small luminescent/magnetic nanocrystals into mesoporous channels or matrices ofmesoporous silica. And core-shell structure is to coat mesoporous silica shell on the surface ofluminescent/magnetic nanoparticle core. Making use of these two structures, we preparedseveral composites. And the textural, morphological and structural properties of thecomposites were carefully characterized by X-ray diffraction, N₂adsorption/desorption,transmission electron microscopy, scanning electron microscopy, photoluminescence spectraand superconducting quantum interference device, respectively. In addition, all thecomposites are employed as drug carries, and the delivery properties are measured by UV/Visabsorption spectroscopy and confocal laser scanning microscopy （CLSM） in vitro and inhuman cells, respectively.Accordingly, we studied the following respects. Firstly, a new family of mesoporous silica microspheres with fibrous morphology （FMSMs） has been successfully synthesizedthrough a facile solvothermal process. The results reveal that FMSMs exhibits interestingfibrous morphology with fibers coming out from the center and distributing uniformly in alldirections. Notably, the open pore channel offers easily accessible high surface area, which iscrucial for mass transport because of the outstanding accessibility to the active sites inside thepores. It implies that FMSMs are prone to load drug molecules. Thus we focused on the drugrelease profiles by tailoring the textural properties of the fibrous mesoporous silica carriers.Secondly, based on FMSMs and embedded structure, a novel fibrous-structuredbifunctional （magnetic and mesoporous） Fe₃O₄/FMSMs microsphere was successfullysynthesized. The method may provide an effective route to fabricate other multifunctionalsilica materials and has an excellent prospect for large scale production. Interestingly,Fe₃O₄/FMSMs consist of fascinating fibrous-structured microspheres with high surface area,and have an average particle diameter of300nm which is within the applicable size for drugand gene delivery. In order to design an ideal material for therapeutics, the unintentionaltoxicity and biocompatibility of the fibrous-structured magnetic and mesoporousFe₃O₄/FMSMs microspheres has been monitored by MTT assay in human adenocarcinomacells. And doxorubicin hydrochloride was employed as a model drug to investigate theintracellular delivery properties of Fe₃O₄/FMSMs sample by confocal laser scanningmicroscopy. Furthermore, utilizing core-shell structure, we prepared Fe₃O₄@mSiO₂magneticcomposite.Thirdly, MCM-48@YVO₄:Eu and Gd₂O₃:Ln@mSiO₂luminescent composites withembedded structure and core-shell structure have been designed respectively. The obtainedmaterials are performed as drug carriers to study the delivery properties of different drugmolecules. The results demonstrated that both the composites possess strong redluminescence of Eu3+. Additionally, the emission intensity of Eu3+increases with the increaseof the cumulative released amount of drug molecules, making the extent of drug release beeasily identified, tracked and monitored by the change of luminescence during the releaseprocess and disease therapy.Finally, combined with embedded structure and core-shell structure, we designedmultifunctional （magnetic, luminescent and mesoporous） Fe₃O₄@mSiO₂@NaYF₄:Yb,Er/Tmcomposites. The use of lower energy infrared light for NaYF₄:Yb,Er/Tm up-conversion phosphors is associated with several significant advantages, such as little photodamage toliving organisms, good biocompatibility, and high excitation-penetration depths in tissues.Many biological samples show autofluorescence under short-wavelength UV radiation, whichgreatly decrease the sensitivity of detection. Furthermore, Fe₃O₄@mSiO₂@NaYF₄:Yb,Erpossesses high saturation magnetization values of38.0emu/g. As the phosphor leaching fromthe surface of the delivery system has direct influence on the utility of the core-shell carrier,some comparable tests were performed.Above all, the structures of embedded structure, core-shell structure and the combinationhave been achieved; the functions of the luminescence and/or magnetism have been integratedwith mesoporous material; and the applications in drug delivery possess sustained release rateand good biocompatibility. Therefore, the research results helped to resolve the problem ofpreparing functional composites directly.