| Over the past decade, cancers have become one of the major causes of mortality in the world. Current clinical therapy methods, including radiation therapy, chemotherapy, hormone therapy and immunotherapy, are often associated with severe side effects. For this reason, there is an urgent need to develop new approaches for cancer treatment. Photothermal therapy(PTT), which emerges in recent years, is considered as a new technique for cancer treatment. PTT specifically ablates the tumor tissues without harming normal tissues. In this paper, Cu3 Bi S3 ternary chalcogenide nanomaterials, which combine diagnosis and therapy functions into one system, were synthesized by using cheap raw materials and simple synthesis method, then the toxicity in vitro and in vivo, CT imaging and PTT effects of the obtained nanomaterials were studied. Then Cu3 Bi S3 nanomaterials were functionalized for multi-mode imaging and PTT functions. The full text is divided into four chapters.In the first chapter, we first introduce some nanomaterials containing metal elements with high atomic number as CT contrast agents for CT imaging. And then the inorganic nanomaterials used as photothermal agents for PTT are summarized, including different structures of gold materials, carbon based nanomaterials, palladium nanosheets, copper sulfide nanomaterials and other new nanomaterials. Finally, the research ideas of this paper were proposed.In the second chapter, we first discuss the influence of different conditions on the size and morphology of the resulting Cu3 Bi S3 nanoparticles, mainly including solvent system, reaction temperature and time, and finally, the optimal conditions for preparing Cu3 Bi S3 were obtained. Then the surface of hydrophobic Cu3 Bi S3 nanoparticles was modified with polyvinyl pyrrolidone(PVP) to produce hydrophilic Cu3 Bi S3/PVP. The methyl thiazolyl tetrazolium(MTT) assay was performed to evaluate the toxicity of Cu3 Bi S3/PVP in vitro, making sure the toxicity of the material is low enough to be used for biological application. In vitro experiments showed that the majority of He La cells can be killed, with cell viability at around 20%. The effect of photothermal therapy in vivo is also remarkable, which indicate that the photothermal effect of Cu3 Bi S3/PVP can effectively inhibit tumor growth. Due to the existence of Bi elements, Cu3 Bi S3/PVP has enhanced X-ray computed tomography imaging(CT imaging) compared with iohexol, a commercial CT imaging contrast agent under the same conditions. Cu3 Bi S3/PVP also has notable CT imaging effect in vivo. Therefore, Cu3 Bi S3/PVP provides a potential platform for the treatment and diagnosis of cancer therapy.The third chapter is based on the second chapter. The Cu3 Bi S3 nanoparticles were further functionalized. Nowdays, nanoparticles having integrated imaging and therapy functions have become a research hotspot, so Cu3 Bi S3 nanoparticles were functionalized for CT imaging, fluorescence imaging and magnetic resonance imaging(MRI). Firstly, Hydrophilic Cu3 Bi S3-PEG-NH2 was obtained by ligand exchange using polyethylene glycol with two amino, then FITC and Gd-DTPA were conjugated through covalent interaction between amino and carboxyl. Preliminary experimental results of in vitro photothermal test, fluorescence imaging and MRI measurement reveal that Cu3 Bi S3-PEG-(FITC&Gd-DTPA) is a multi-functionalized nanomaterial of multi-mode imaging and PTT, having potential applications in biomedicine.Chapter IV mainly summerizes important results of this thesis, and then presents the remaining issues and future research directions of inorganic nanoparticles as photothermal agents. |
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