用于肿瘤治疗的热种子材料与金磁纳米材料的制备与性能研究

发布时间：2018-12-12 06:55

【摘要】：Fe304为基础的热种子材料Fe3O4@CNTs (Fe3O4包覆CNTs)与金磁纳米材料Au@Fe3O4 (Au包覆Fe3O4),均具有良好的生物稳定性、生物相容性、无毒性和磁靶向特性,因此在肿瘤治疗等生物医学领域得到广泛的应用。其中,热种子材料Fe3O4@CNTs主要应用于肿瘤热疗,金磁纳米材料Au@Fe304则在肿瘤化疗中作为靶向药物载体得以应用。然而,应用过程发现,对热种子材料Fe3O4@CNTs,碳纳米管表面的Fe3O4的包覆情况及包覆完成后的分散情况,以及磁性纳米颗粒所需的最适宜铁碳比等问题,都会对肿瘤热疗产生重要影响；同样,对金磁纳米材料Au@Fe3O4, Fe3O4纳米微球的成形性、Au纳米粒子对Fe3O4表面包覆性能、以及粒子团聚和分散性不好等问题,也会严重影响其作为肿瘤化疗中的靶向药物载体的应用。而且,由于金磁纳米材料Au@Fe3O4本身不具有可供检测的荧光性能,这就使该材料的应用受到了一定程度的限制。因此,优化两种材料的制备技术,探究可供示踪检测用的Au@Fe3O4生物材料是一项极具实用价值和挑战性的工作。本文利用化学沉淀法制备了形貌均一、分散性良好、包覆均匀的热种子材料Fe3O4@CNTs;利用聚乙二醇为分散剂,水热法制备了尺寸适宜、成形良好、分散性良好的纳米级Fe3O4微球；利用晶种生长法制备了包覆均匀、分散性良好的金磁纳米材料Au@Fe3O4,并在此基础上利用溶胶凝胶法制备得到Au@Fe3O4/YVO4:Yb3+,Er3+荧光纳米粒子,为探究Au@Fe3O4在生物体内的流转和沉积提供了研究基础和技术准备。通过XRD、TEM、SEM、FTIR和荧光分析等表征手段,研究了几个影响因素对制备结果的影响,并对其物相组成、结晶性、微观形貌和荧光性能进行了分析。本文的主要研究内容及结果如下：(1)通过化学共沉淀法制备得到热种子材料Fe3O4@CNTs,并分别探讨了研究过程中加入不同质量的碳纳米管和不同种类的表面活性剂对样品性能的影响。结果发现,在相同的表面活性剂和相同的研究条件下,碳纳米管含量为12.5%时,铁氧体在碳纳米管表面包覆的最好,最为均匀。在碳纳米管含量均为12.5%和相同的研究条件下,十六烷基三甲基溴化铵(CTAB)作为表面活性剂制得样品的性能要优于十二烷基硫酸钠(SDS)和壬基酚聚氧乙烯醚(IGO)作为表面活性剂制得的样品。因此,最佳工艺参数为CNTs含量为12.5%,并选用CTAB为表面活性剂。此时,碳纳米管的表面包覆均匀,磁饱和强度也达到了肿瘤靶向热疗的要求。(2)以聚乙二醇为分散剂,水热法制备的Fe3O4为原料,利用晶种生长法制备得到金磁纳米材料Au@Fe3O4,并探讨了Fe3O4添加量,即铁金比对样品制备的影响。结果表明,以PEG200为分散剂,可以制备出粒径为300-400nm左右,呈均匀球状的Fe3O4纳米颗粒；Fe3O4添加量过多、铁金比过大时,纳米Au颗粒太少而不足以完成包覆,会存在很多裸露的Fe3O4；而Fe3O4添加量过少、铁金比过小时,纳米Au颗粒太多,会在Fe3O4表面发生团聚,包覆不均匀；只有当Fe3O4添加量适中、铁金比恰当时,纳米Au颗粒才可以较为均匀地包覆在Fe3O4的表面。通过对比研究得出,最为适合的Fe3O4添加量为0.03g,即：Fe3O4:Au=3:8时可以满足纳米Au颗粒对Fe3O4纳米微球的均匀包覆。(3)以硝酸镱、硝酸铒和钒酸钇为原料,柠檬酸为络合剂,在溶胶凝胶法制备YVO4:Yb3+,Er3+荧光纳米粒子过程中加入已制备好的Au@Fe3O4,制备得到Au@Fe3O4/YVO4:Yb3+,Er3+荧光纳米粒子。SEMs XRD测试表明,在Au@Fe3O4的表面沉积YVO4:Yb3+,Er3+上转换荧光纳米粒子对金磁纳米材料Au@Fe3O4的晶体结构和稳定性没有影响；而且,Au@Fe3O4/YVO4:Yb3+,Er3+样品在980nm激光激发下,会发射出明显的绿色荧光。总之,本文成功制备了荧光纳米粒子Au@Fe3O/YVO4:Yb3+,Er3+,为后续实现金磁纳米材料Au@Fe3O4在动物体内的示踪提供了材料基础。
[Abstract]:The Fe-304-based thermal seed material Fe3O4@CNTs (Fe3O4-coated CNTs) and the gold-magnetic nano-material Au@Fe3O4 (Au-coated Fe3O4) have good biological stability, biocompatibility, non-toxicity and magnetic targeting characteristics, and are widely used in the fields of biomedicine such as tumor treatment and the like. The Fe3O4@CNTs of the thermal seed material is mainly used for tumor thermal therapy, and the Au@Fe304 of the gold magnetic nano-material is used as a target drug carrier in the tumor chemotherapy. however, in that application process, the problem of the Fe3O4@CNTs of the hot seed material, the coating condition of Fe3O4 on the surface of the carbon nano tube and the dispersion condition after the coating are completed, as well as the most suitable iron-to-carbon ratio required by the magnetic nano-particles, can have an important effect on the heat treatment of the tumor, The Au@Fe3O4 of the gold-magnetic nano-material, the forming property of the Fe3O4 nano-ball, the coating performance of the Au nano-particles on the surface of the Fe3O4, the agglomeration and the poor dispersibility of the particles and the like can also be seriously affected as the application of the targeting drug carrier in the tumor chemotherapy. Moreover, since the gold magnetic nano-material Au@Fe3O4 itself does not have the fluorescence property that can be used for detection, the application of the material is limited to a certain degree. Therefore, to optimize the preparation technology of two materials, it is a practical and challenging work to explore the Au@Fe3O4 biological material that can be used for trace detection. The chemical precipitation method is used to prepare the hot seed material Fe3O4@CNTs with uniform morphology, good dispersibility and uniform coating, and the nano-scale Fe3O4 micro-spheres with proper size, good shape and good dispersivity are prepared by using the polyethylene glycol as the dispersing agent and the water heat method. The gold magnetic nano-material Au @ Fe3O4 with uniform and good dispersibility is prepared by the crystal seed growing method, and the Au @ Fe3O4/ YVO4: Yb3 +, Er3 + fluorescent nano-particles are prepared by the sol-gel method. In order to study the flow and deposition of the Au@Fe3O4 in the living body, the research foundation and the technical preparation are provided. The influence of several factors on the preparation results was studied by means of XRD, TEM, SEM, FTIR and fluorescence analysis. The main contents and results of this paper are as follows: (1) The Fe3O4@CNTs of the hot seed material is obtained by the chemical co-precipitation method, and the effect of different quality carbon nanotubes and different kinds of surfactant on the performance of the sample is also discussed. The results show that, under the same surface active agent and the same research condition, the content of the carbon nano-tube is 12.5%, the best and the most uniform of the ferrite on the surface of the carbon nano-tube. The performance of CTAB as a surfactant was superior to that of sodium dodecyl sulfate (SDS) and nonylphenol polyoxyethylene ether (IGO) as a surfactant under the same study conditions. Therefore, the optimum process parameters were CNs content of 12.5% and CTAB as the surface active agent. At this time, the surface of the carbon nanotube is uniformly coated, and the magnetic saturation intensity also reaches the requirement of the tumor targeted thermal therapy. (2) The Au@Fe3O4 of the gold-magnetic nano-material was prepared by using the Fe3O4 as the dispersing agent and the hydrothermal method, and the effect of the addition amount of the Fe3O4, that is, the iron-to-gold ratio on the preparation of the sample, was also discussed. The results show that the nano-Au particles with the particle size of 300-400nm can be prepared by using the PEG200 as the dispersing agent, and the Fe3O4 nano-particles with uniform spherical shape can be prepared; the addition amount of the Fe3O4 is too large; when the iron-to-gold ratio is too large, the nano-Au particles are too small to complete the coating, so that a plurality of bare Fe3O4 is present; and the addition amount of the Fe3O4 is too small, When the iron-gold ratio is more than an hour, the nano-Au particles are too large to be agglomerated on the surface of the Fe3O4, and the coating is not uniform; only when the addition amount of the Fe3O4 is moderate and the iron-gold ratio is appropriate, the nano-Au particles can be more uniformly coated on the surface of the Fe3O4. The results show that the most suitable Fe _ 3O _ 4 is 0. 03g, that is, Fe3O4: Au = 3: 8, which can satisfy the uniform coating of the nano-Au particles on the Fe3O4 nano-spheres. and (3) adding the prepared Au@Fe3O4 into the process of preparing the YVO4: Yb3 +, Er3 + fluorescent nano-particles by using the nitric acid solution, the nitric acid salt and the ferroic acid as the raw material and the citric acid as a complexing agent, and preparing the Au@Fe3O4/ YVO4: Yb3 +, Er3 + fluorescent nano-particles. The SEMS XRD test shows that the conversion of the fluorescent nanoparticles on the surface of the Au@Fe3O4 has no effect on the crystal structure and the stability of the Au@Fe3O4 of the gold-magnetic nano-material; moreover, the Au@Fe3O4/ YVO4: Yb3 + and Er3 + samples are excited by a 980nm laser, a clear green fluorescence is emitted. In conclusion, the Au@Fe3O/ YVO4: Yb3 + and Er3 + of the fluorescent nano-particles were successfully prepared in this paper, which provided a material basis for the follow-up of the Au@Fe3O4 of the gold-magnetic nano-material.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：TB383.1

【参考文献】