Study On Construction And Properties Of Magnetic Core@Shell Multifunctional Drug Carriers

In the field of the anti-tumor research currently, a single treatment method often has been unable to achieve and satisfy the requirement of treatment. The traditional radiotherapy and chemotherapy treatment also produce great toxicity and damage to normal tissues. Therefore, the synergy therapy treatment combined with a variety of novel treatments (like photo-thermal therapy and photodynamic therapy), and application of targeting drug carrier with sensitive release performance, which could change the way of drug dosage, delay the generation of drug resistance, and reduce the toxicity of anticancer drugs on normal tissue, improve drug stability and bioavailability, has become one of the current hot spots in the research of the anticancer field. Therefore, this thesis aims to the preparation and synergy anticancer effect of several mutil-functional drug carriers. The main research contents of the thesis are as below:1. In this work, the magnetic oxide (Fe3O4)@metal-organic frameworks (MOF) @hydroxyapatite (HAp) nanocomposite microspheres were prepared via a solvo-thermal reaction. Firstly, the Fe3O4 nano-microspheres were prepared and served as the magnetic cores. Then, Fe3O4@Fe-MOF was obtained by the self-assembly of Fe-MOFs with porous structure on the surface of magnetic cores. Finally, the green biological molecule phytic acid (IP6) was used as the template and the initial source of phosphorus, and the urea as the pore-forming agent and pH regulation substance to prepare HAp shell, which was further coated on Fe3O4@Fe-MOF for the formation of the Fe3O4@Fe-MOF@HAp nanocomposite microsphere. The anti-cancer drug doxorubicin hydrochloride (DOX) could be effectively loaded on Fe3O4@Fe-MOF@HAp nanocomposite microspheres with the drug loading capacity up to 32.96 ?g/mg. The nanocomposite microspheres with the saturation magnetization of 34 emu/g can effectively achieve the magnetic targeting. In addition, the HAp shell with favorable biocompatibility and pH response characteristics which could be used to control the release of loaded DOX from Fe3O4@Fe-MOF@HAp nanocomposite microspheres at the acidic environment of the simulated tumor cell region, which could effectively kill tumor cells and reduce the toxic side effects on normal tissue.2. In this chapter, the prepared Fe3O4 nano-particles was used as magnetic cores, with the simultaneous addition of gold nanoparticles and HCl solution, the Fe3O4 nano-particles were slowly eroded and released Fe3+ ions. These Fe3+ ions initiated the polymerization of pyrrole (Py) into polypyrrole (PPy) around the Fe3O4 and Au nano-particles. Thus the core-shell Fe3O4@Au/PPy composite nanometer microspheres were prepared. The results show that the Fe3O4@ Au/PPy composite carrier can effectively load DOX, the loading efficiency of DOX reaches 46.84 ug/mg. And the saturation magnetization of nanocomposite microsphere is 20 emu/g with the characteristics of magnetic targeting. We also found that Fe3O4@Au/PPy composite microspheres exhibit good photo-thermal effect and induced performance for the generation of singlet oxygen. The prepared novel drug carrier could achieve enhanced treatment for tumor cells by combining chemotherapy, photodynamic therapy with photo-thermal therapy. Moreover, the targeting characteristic of magnetic Fe3O4 can significantly further improve antitumor efficiency and reduce the side effects to normal tissues.3. In this part, a novel core-shell Fe3O4@MoS2@ZnO magnetic nano-scaled composite microsphere has been successfully prepared in a facile one-step hydrothermal method. The results show that the constructed nano-carriers exhibit high DOX loading capacity of 68.14 ?g/mg and saturation magnetization of 45 emu/g, which could effectively deliver drug to tumor lesion site under the action of magnetic targeting and reduce the side effect on the normal cells and tissues. Moreover, the photo-thermal efficiency contributed by the MiS2 nano-flakes under 808-nm NIR laser irradiation in the Fe304@MoS2@ZnO composite were utilized for realizing effective photo-thermal therapy (PTT) of cancer. Finally, the ZnO shell as a "door gate" could achieve the pH controlled multi-release of photo-thermal materials and drugs. Thus, the Fe3O4@MoS2@ZnO composite microspheres not only have effective magnetic targeted PTT to cancer cells but also can load the anti-cancer drug DOX to achieve the enhanced antitumor effect through the combination of chemotherapy and PTT.