| 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. The green biological molecules 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 substances to prepare HA hollow microsphere by the hydrothermal method. And by means of surface modification of L-cysteine, the prefabricated Au nanorods (AuNRs) could combine with the HA microsphere for the formation of the hollow HA/Au nanocomposite microsphere. The anti-cancer drug doxorubicin hydrochloride (DOX) could be effectively loaded on HA/Au composite carrier. The HA/Au-DOX composite possessses excellent biocompatibility and pH response characteristics of HA and could gradually decompose for the controlled-release of DOX in tumor cells with acidic condition. In the meantime, the AuNRs on the surface of composite microsphere can play the role of photo-thermalagent under the irradiation of near infrared light. The antitumor ability of system could be enhanced by the collaborative effect of chemotherapy and photo-thermal therapy.2. The chemotherapy drugs have a lot of toxic and side effects on normal cells and tissues. Therefore, introducing the targeting mechanism is necessary during the process of anti-tumor treatment. In this part, firstly the magnetic Fe3O4 nanomicrospheres with porous structure were prepared. Then the precasted nitrogen-doped carbon quantum dots (N-CDs) with photo-thermal effect were loaded in the pores or on the surface of Fe3O4. Lastly, the HA shell formed on the surface of porous Fe3O4 nanospheres. Thus the core-shell N-CDs@Fe3O4@HA composite nanometer microspheres were prepared. The HA shell was not only used to load the anti-cancer drug 5-fluorouracil (5-FU), but also could be acted as a kind of controlled gate, to close the porous N-CDs@Fe3O4 microsphereand allowed the release of 5FU and N-CDs at acid environment of tumor. The prepared novel drug carrier could achieve the treatment of multi-level release of drugs and the enhanced antitumor effect by combining chemotherapy with photo-thermal therapy. Moreover, the targeting characteristic of magnetic Fe3O4 can significantly improve antitumor efficiency and reduce the side effects to normal tissues.3. A sandwich-like rGO/Fe3O4@mSiO2 composite is constructed using the electrostatic adsorption principle. Under the stress of silica on both sides, this "sandwich" structure can effectively reduce the surface energy between the layers of the middle graphene layer, thus the aggregation of graphene sheets could be hinder greatly, which could be benefical to the dispersion of tissue fluid. At the same time, the mesoporous structure silica has a large number of pores and could greatly increase the loading of 5-FU in the rGO/Fe3O4@mSiO2 composites. The magnetic targeting characteristic of Fe3O4 nanoparticles can also make drug carrier arrive at the tumor areas quickly and efficiently, and greatly improve the therapeutic efficacyfor tumor. And the rGO component has good photo-thermal effect, can undertake the photo-thermal treatment on tumor cells, to achieve the synergy effects of treatment with chemotherapy. |
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