基于功能化介孔氧化硅纳米材料的制备及其生物应用

发布时间：2018-01-16 07:10

本文关键词：基于功能化介孔氧化硅纳米材料的制备及其生物应用　出处：《福建农林大学》2017年硕士论文　论文类型：学位论文

【摘要】：纳米材料,由于具有较大的比表面积、可修饰性强,并与蛋白质分子处在同一尺度范围等优点,在肿瘤等重大疾病治疗中具有广泛应用。但是由于肿瘤疾病的复杂多样性和易转移等特点,具有单一治疗功能的纳米材料,如基于化疗药物负载的单一纳米材料等,已不能满足肿瘤疾病治疗的需求,因此研发一种基于化疗、光动力学治疗和光热治疗等于一体的多功能纳米药物非常迫切。介孔二氧化硅纳米材料,由于其具有可操作性强、具有大的比表面积和丰富的孔道结构,并且生物相容性好等优点,能够满足构建集化疗、光动力治疗和光热治疗于一体的纳米药物的要求。本论文,以介孔二氧化硅纳米材料为框架,通过碳量子点的包埋和孟加拉玫瑰红光敏剂的掺杂,及化疗药物阿霉素的负载构建出一种集化疗、光动力治疗于一体的肿瘤治疗药物。首先,研究了核壳结构介孔二氧化硅纳米颗粒的制备;然后通过原位包埋的方法实现了碳量子点和光敏剂在介孔二氧化硅中的负载,同时对此材料的光学特性、稳定性及单线态氧产率进行了详细地研究分析,并对此材料化疗药物的负载及药物的可控释放进行了分析评估;在此基础上,对此复合药物的肿瘤治疗效果及抑菌效果进行了验证评估。其主要研究成果如下:(1)采用微乳液法制备出不同尺寸的介孔二氧化硅纳米颗粒。通过对反应时间、温度及硅源变化的调控,研究了介孔二氧化硅的尺寸、孔径大小与反应温度、硅源、表面活性剂等的关系;同时通过氮气吸脱附等表征手段对所得纳米材料进行详细表征。最终,我们得到了 79±2.7 nm,孔径为2 nm的介孔二氧化硅核;并通过外延生长的方法得到了 104±6.0nm,孔径为3nm的单分散的具有核壳结构的介孔二氧化硅纳米材料。(2)多功能介孔纳米药物的制备表征。利用两步法得到核壳结构介孔二氧化硅纳米颗粒,并通过原位包埋的方法将碳量子点、孟加拉玫瑰红分别包埋在核壳二氧化硅的核和壳层中,得到了集光动力学治疗和跟踪监测为一体,同时能进一步负载化疗药物的多功能介孔纳米药物。然后对此纳米药物的光学特性、单线态氧产率、化学药物负载率和负载量等进行了详细的表征分析。(3)多功能介孔纳米药物的肿瘤治疗和抑菌研究。利用碳量子点的荧光特性,研究分析了此材料的细胞共聚焦成像效果;然后通过体外细胞实验,对此材料癌症光动力学治疗效果进行了详细的调研,此材料在100μg/mL便能够杀死90%以上的癌细胞(细胞:H1299);说明了此材料有较好的光动力学治疗效果;同时,进一步负载化疗药物,调研了此多功能纳米材料的抗癌效果,在30 μg/mL时便能杀死90%以上肿瘤细胞,说明了将光动力治疗和化学药物治疗联合能有效地提高肿瘤的治疗效果。同时,利用此材料的光动力学治疗能力,并负载抗菌药物氨苄青霉素,进一步调研了此材料的抑菌能力;在光照条件下,载药纳米材料的浓度为100μg/mL时,能够完全抑制大肠杆菌的生长。通过以上研究说明本论文所构建的基于介孔二氧化硅的多功能纳米药物在肿瘤治疗和细菌抑制中有较理想的效果,此材料作为一种新型的抗癌药物和抑菌药物在肿瘤治疗和抑菌等方面有很大的应用潜力。
[Abstract]:Nano materials, due to its large specific surface area, modification ability, and in the same scale and other advantages of protein molecules, is widely used in the treatment of cancer and other major diseases. But due to the complexity and diversity of the tumor and metastasis characteristics of nano material with a single treatment function, such as chemotherapy drug loading single nano materials, has been unable to meet the demand of the treatment of tumor diseases, therefore the development of a multifunctional nano drug based chemotherapy, photodynamic therapy and photothermal therapy is one of the very urgent. The mesoporous silica nano material, because of its strong maneuverability, with large surface area and rich the pore structure, and has the advantages of good biocompatibility, can meet the construction set of nano drug chemotherapy, photodynamic therapy and photothermal therapy in one of the requirements. In this thesis, the mesoporous oxide two Silicon nano materials as the framework, the carbon quantum dots embedded and Rose Bengal sensitizer doping, and adriamycin load to construct a set of chemotherapeutic drugs for the treatment of cancer, photodynamic therapy in one. First, study the core-shell structure of mesoporous silica nanoparticles were prepared by in-situ method; then embedding the carbon quantum dots and photosensitizer loaded in mesoporous silica, and optical properties of this material, and the stability of singlet oxygen yield in detail, and the controlled release of drug loading and drug materials were analyzed on the basis of this evaluation; compound drugs therapeutic effect and antibacterial effect was verified by assessing. The main results are as follows: (1) prepared by microemulsion method mesoporous silica nanoparticles of different sizes. The anti We should control time, temperature variation and silicon source, the mesoporous silica size, pore size and reaction temperature, silicon source, surfactant and so on; at the same time through nitrogen adsorption desorption were characterized by means of detailed characterization of the nano materials. Finally, we got 79 + 2.7 nm, aperture mesoporous silica core 2 nm; and through the epitaxial growth method was 104 + 6.0nm, diameter 3nm of monodisperse core-shell mesoporous silica nanomaterials. (2) characterization of preparing multifunctional mesoporous nanoparticles. By two steps the core-shell structure of mesoporous silica nanoparticles particle, method and by in situ encapsulated carbon quantum dots, Rose Bengal were embedded in the nuclear shell and core-shell silica, obtained in photodynamic therapy and monitoring as a whole, and can be further supported multi drug treatment The function of mesoporous nano drug. Then the optical properties of nano drug, singlet oxygen yield, chemical drug loading rate and loading were analyzed and characterized in detail. (3) tumor treatment and antibacterial activity of multifunctional mesoporous nano drug. Using fluorescence characteristics of carbon quantum dots, research and analysis of this material cell confocal imaging effect; then through in vitro experiments, this material for cancer photodynamic therapy effect was investigated, the material will be able to kill more than 90% of cancer cells in 100 g/mL (H1299 cells); that this material has better effect of photodynamic therapy; at the same time, further load chemotherapy. Investigation of the anticancer effect of the multifunctional nano materials, in 30 g/mL can kill more than 90% of the tumor cells, that the photodynamic therapy and chemotherapy combination can effectively improve the treatment effect of tumor Fruit. At the same time, the use of photodynamic therapy ability of this material, and the load of antibiotics ampicillin, further investigation of the antibacterial activity of this material; under the condition of light, the concentration of drug loaded nanoparticles is 100 g/mL, which can completely inhibit the growth of Escherichia coli. Through the above research that constructed in this paper multifunctional nano mesoporous silica based drug in the treatment of cancer and bacterial inhibition has an ideal effect, this material as a new type of anticancer drugs and antimicrobial drugs have great potential application in cancer therapy and antibacterial and other aspects.

【学位授予单位】：福建农林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TB383.1;R730.5

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