| Multifunctional nanocarrier systems can combine functions of diagnostic imaging, targeted delivery of anticancer drugs and combination therapy, which not only can improve the anti-tumor effect, but also can reduce the damage to normal tissues and organs. Therefore, multifunctional nanocarrier systems have great potential application in tumor diagnosis and treatment. It has been found that Fe3O4 magnetic nanoparticles have the characteristics of low toxicity, superparamagnetism and good photothermal conversion performance. The multifunctional nanocarrier system with magnetic targeting and photothermal performance can be constructed by the modification of Fe3O4 magnetic nanoparticles.DOX is a kind of antitumor drug widely used in clinical treatments, and the severe side effects greatly limit its application. This experiment used the as-prepared magnetic nanoparticles loading DOX to construct thermo-sensitive nanocarrier drug delivery system that triggered by NIR. After DOX was targeted to the tumor site, the drug was released by employing the NIR to irradiate the tumor site. This drug delivery system combined photothermal therapy with chemotherapy, and meanwhile improved the therapeutic effect.This paper constructed a thermo-sensitive magnetic nanocarrier drug delivery system, which possessed good superparamagnetism, photothermal conversion properties and biocompatibility. Then DOX was loaded onto the carriers via covalent bonds to construct Fe3O4-Azo-DOX drug delivery system, and then the Fe3O4-Azo-DOX with high stability, NIR sensitivity and low toxicity was applied to the study of chemo-photothermal tumor therapy in vitro and vivo. Concrete study content as follows:In Chapter 2, the Azo-functionalized Fe3O4 nanoparticles were prepared, and their relevant natures were characterized. The results showed that Fe3O4-Azo nanoparticles had magnetism and superparamagnetism, thus can be used in magnetic targeting and MRI. Also, it had good photothermal conversion performance, which could absorb NIR to generate heat quickly. The MCF-7 breast cancer cell was selectedas the model to investigate the cytotoxicity of Fe3O4-Azo nanoparticles, and the experiment result demonstrated that the Fe3O4-Azo nanoparticles with excellent biocompatibility could be used as drug carriers.In Chapter 3, DOX was loaded onto Fe3O4-Azo nanoparticles to construct the NIR triggered drug delivery system. According to the study of NIR triggered DOX release from Fe3O4-Azo-DOX in different pH conditions, it could be seen that the drug delivery system was NIR responsive and showed the best drug release behavior in pH 5.7. The anti-tumor study of Fe3O4-Azo-DOX in vitro proved that chemo-photothermal therapy was obviously superior to single photothermal therapy based Fe3O4-Azo and single chemotherapy based free DOX.In Chapter 4, the Fe3O4-Azo-DOX showed higher stability and NIR sensitivity in compare with Fe3O4-DOX that constructed via non-covalent bonds in the study of stability and drug release properties. The cellular uptake and cytotoxicity experiments further proved this conclusion. Besides, the in vivo cardiotoxicity evaluation verified that Fe3O4-Azo-DOX had higher stability and lower systemic toxicity than Fe3O4-DOX.In the last chapter, the in vivo anti-tumor effect of Fe3O4-Azo-DOX was studied.Based on the in vivo investigation of distribution, photothermal performance and MRI,the tumor inhibition efficiency of Fe3O4-Azo-DOX was evaluated. And the result of in vivo experiment exhibited that chemo-photothermal therapy was obviously superior to single photothermal therapy and single chemotherapy. In addition, the evaluation of histological analyses demonstrated that Fe3O4-Azo-DOX had no significant toxicity to normal tissues during the course of therapy. |
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