The Construction Of Multifunctional Mesoporous Material Drug-carrying System And Its Preliminary Medical Application

The chemotherapy of cancers mainly applies drugs to kill or inhibit the proliferation of cancer cells.Due to the similarity between normal cells and cancer cells,the use of drugs may cause some toxic effects on normal cells.In recent years,the construction of intelligent responsive drug release system by stimulating responsive materials as a blocking device of functionalized mesoporous materials has become prevalent in the biomedicine and pharmaceutical fields.However,the current stimuli-responsive drug delivery systems may suffer from poor biocompatibility,low drug loading efficiency,premature drug release,and single therapeutic effect,which may limit their large-scale applications.Therefore,it is of great significance to establish a multimodal system that integrates the multiple therapies in one nanoplatfom.Aiming to develop some responsive multi-functional drug delivery systems with mesoporous materials,this thesis has mainly carried out the following research works:?1?A multifunctional drug-loading system has been developed with complex-encapsulated mesoporous silica?MSN@MPN?for the selective drug release and photothermal synergetic therapy?Chapter 2?.In this system,natural tannic acid crosslinking with metal ions was coated onto the surface of MSN,serving as a gate keeper to encapsulate the chemical drugs in the mesopores of the MSN.Under the neutral conditions,the gate keeper can effectively block the mesoporous structure of MSN so as to prevent the release of chemical drugs.Under acidic conditions,the gate keeper would be degraded to trigger the release of chemical drugs.At the same time,the complexe formed by iron ions crosslinking with tannic acid can present the better photothermal conversion performance so as to be used as a reagent for photothermal therapy.In this work,systematic investigations are conducted on the stimuli-responsive drugs release behavior and the photothermal conversion property of the mesoporous silica drug-loaded system.The results show that the nanosystem can possess the favourable photothermal conversion performance and excellent pH-stimulated responsive drug delivery property.The data of CCK-8 experiments indicate that the nanosystem loaded with chemical drugs can effectively inhibit the proliferation of lung cancer cells,and laser irradiation can significantly enhance the inhibitory effect on lung cancer cells.This synergetic photothermal and drug-loading system of mesoporous silica may promise an ideal stimulus-responsive drug delivery therapy system.?2?A pH-stimuli responsive drug delivery system has been proposed using complex-coated mesoporous iron oxide?Fe₃O₄??chapter 3?.On the one hand,the metal-tannic acid complex can block the mesoporous structure of Fe₃O₄ to avoid premature release of drug;on the other hand,mesoporous Fe₃O₄ can exhibit the excellent photothermal conversion performence that can be used as a photothermal conversion material for the photothermal therapy.Therefore,an intelligent synergistic therapy system integrating pH-stimulated responsive drug release and photothermal therapy has been constructed.Mesoporous Fe₃O₄ materials were characterized by scanning electron microscopy,transmission electron microscopy,x-ray diffraction,and physical adsorption analyzers.Also,the photothermal conversion performance of the nanosystem was investigated by laser irradiation at 808 nm.Besides,the pH-stimulated responsive release behavior was explored in the buffer conditions.The results show that the developed drug-release system can selectively release chemical drugs through the pH-stimuli of the microenvironment.The significant increase in the temperature can also be expected for the system under the laser irradiation,thus holding great promise for the wide applications as a new stimulated responsive drug targeted and photothermal therapy candidate.