| In recent years, cancer has become one of the main threats for humanity. In order to cure cancer effectively, target positioning, high load and effectively controlled release drugs become a hot research topic. Using ferroferric oxide and other magnetic nanoparticles as a targeted materials research has also tends to be mature. Meanwhile, there has been lots of research using functional mesoporous silica and macroporous materials to load drugs. To release drug effectively, one must pass a certain way of releasing drugs into the lesions effectively, and at the same time reduce the toxicity to normal cells. The controlled releasing of drug includes response in vitro release and in vivo release. Due to the interoperability and exactly sensitive controllability of the release in vitro response has caused the great interest of the researchers.Therefore, in order to achieve drug targeting orientation, effectively drug load and the microwave controlled release, this study used the microwave thermal response. It is a uniform heating, good thermal stability and high safety to implement drug microwave controlled release. On the basis of magnetic targeting and mesoporous silica to load drugs of Fe3O4@mSiO2-APTES, the dissertation introduced WO3, ZnAl2O4 and ZnWO4 for the first time to study the drug load and the microwave controlled release. Meanwhile, it explored the interaction between drugs and nanocarrier by using microcalorimetric. Compare the difference of interaction for hydrophobic and hydrophilic medications with the same nanocarrier. Then it provided the theoretical guidance of choosing condition for microwave controlled release. The dissertation includes the following five parts:1. The dissertation prepared an amino functional Fe3O4@nSiO2@mSiO2-APTES nanoparticle by wet chemical method with anti-cancer drugs etoposide (VP16) as model drug. For the first time it investigated the thermodynamic and kinetic properties for the drug-loading and release processes using microcalorimetry. The drug-loading processes were exothermal and the release process was endothermal. A series of thermodynamics parameters ?H, ?S and ?G for drug-loading and release process were calculated. For drug-loading processes, the critical value was determined, the kinetics equation d?/dt=10-3.66(1-a)1.01, and rate constant k=10-3.66s-1 were also obtained. The results show that the interaction force between drug molecular and nanocarrier is hydrogen-bond interaction which was derived from the experimental values of the molar enthalpies (?H< 0) and molar entropy (?S<0). The dynamic results show the drug loading process is a pseudo first order reaction in a spontaneous process. It therefore promises to provide theoretical basis for the interaction between drug molecular and nanocarrier, so as to guide externally controlled drug-delivery system in cancer therapy.2. The dissertation constructed a novel WO3 interlayered Fe3O4@WO3@mSiO2-APTES core-shell structured drug nanocarrier to investigate loading and controllable release properties of etoposide (VP16). This nanocomposite composed of mesoporous silica (mSiO2) shell with magnetic Fe3O4 core, WO3 interlayer. They possess high surface area of 234.5 m2/g, provide large accessible pore volume of 0.14 cm3/g for adsorption of drug molecules, high magnetization saturation value of 39.9 emu/g for drug targeting under foreign magnetic fields, relatively higher reflection loss of -22.75 dB for controlled release by microwave-triggered which was caused by WO3 interlayer. The VP16 release of over 85.69% under microwave discontinuous irradiation outclasses the 15.88% within 600 min only stirring release. This multifunctional material shows good performance for targeting delivery and WO3 microwave controlled release of anticancer drugs based on all the properties they possess.3. The dissertation constructed a micro wave-targeted-fluorescence multifunctional Fe3O4@ZnAl2O4:Eu3+@mSiO2-APTES core-shell nanocarrier. The Fe3O4 core can target the anticancer drug to the lesion location with a relatively high magnetization of 17.4 emu/g. The ZnAl2O4:Eu3+ interlayer will be acted as microwave absorber and possessed fluorescence luminous performance. The mesoporous shell can load drugs effectively with a large surface area of 518.60 cm2/g, uniform accessible mesopores of 2.43 nm, large accessible pore volume of 0.275 cm3/g. Drug release processes were studied under microwave discontinuous irradiation and only stirring release as a cycle. There were over 78.2% VP16 molecular were released after seven cycles. It also be investigated that this nanocarrier appear the Eu3+ energy level transition of 5Do?*7Fj (j=0,1,2,3,and 4) in 576, 589,611,649 and 699 nm under the 398 nm excitation light. This proved that this nanocarrier has fluorescence luminous performance and can be used clinically for in vivo fluorescence monitoring. It indicated that this multifunctional material showed a good performance for targeting delivery and ZnAl2O4:Eu3+ microwave controlled release of anticancer drugs. Meanwhile it has fluorescent monitoring performance for fluorescence detection on clinic.4. The dissertation introduced ZnWO4 which possess microwave absorbing properties and autofluorescence properties simultaneously and constructed a microwave-targeted-fluorescence multifunctional Fe3O4@ZnWO4@mSiO2-APTES core-shell nanocarrier. The mesoporous shell can load drugs effectively with a large surface area of 325.28 cm2/g, uniform accessible mesopores of 2.42 nm, large accessible pore volume of 0.148 cm3/g. The Fe3O4 core can target the anticancer drug to the lesion location with a relatively high magnetization of 37.2 emu/g. It studied drug release processes under microwave discontinuous irradiation and only stirring release as a cycle. Over 72% VP16 molecular were released after seven cycles. Meanwhile, the nanometer carrier created maximum absorption at 465 nm under the 282 nm excitation light. It is proved that the carrier has fluorescence luminous performance and can be used for in vivo fluorescence monitoring on clinical. The results confirmed that the study has prepared a microwave-targeted-fluorescence multifunctional and simple structure nanocarrier.5. The dissertation chose the Fe3O4@ZnWO4@mSi02-APTES nanopartical as the carrier which possess a simple structure, microwave-targeted-fluorescence properties. It also chose the hydrophilic drugs (Oxysophocarpine and Doxorubicin hydrochloride) and hydrophobic drugs (Etoposide and Cisplatin) as the template drugs. Then it studied the drug loading and releasing process of these four drugs with nanocarrier, as well as investigated the difference interaction between them. The results showed that it was hydrogen bond interaction between hydrophilic drugs (Oxysophocarpine and Doxorubicin hydrochloride) and nanocarrier, but it was van der Waals force between hydrophobic drugs (Etoposide and Cisplatin) and nanocarrier. It is suggested that the different forces for the two types drugs could provide theoretical guidance for microwave drug controlled release and choose the release condition. |
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