基于多功能核—壳结构纳米粒子的双重响应药物控释与光动疗研究
发布时间：2018-10-21 13:16
【摘要】：传统的癌症治疗方法有疗效低,疗程长,成本高,治疗风险较大等不利的缺点,现今研究工作者专注于开发新型的癌症治疗手段用以克服这些缺点,新型手段中最受关注的就包括纳米粒子靶向给药技术;已有的研究成果中的纳米粒子可以实现载药放药或者光动疗等技术,而处于研究前沿的新一代载药纳米粒子可以整合载药、外部响应控制放药、特异性靶向、生物成像、体内诊断以及光动疗等多种作用为一体,制备出多功能新型纳米粒子。本文的主要研究内容旨在设计一种尺寸小于100nm且具有载药、p H响应放药、光动疗、特异性靶向及生物成像功能的纳米粒子,并着重研究p H刺激响应的药物控释及光动疗性能,以实现在体内酸性环境以及体外近红外光光照的双重刺激下达到药物控释和单线态氧光动疗的双重响应,以实现鸡尾酒疗法。在制备方面,本文通过热裂解法及溶胶凝胶法,合成并组装三层核-壳-壳结构的UCNP@SiO_2(MB)@m SiO_2介孔纳米粒子,通过内核的镧系元素离子掺杂上转换纳米粒子NaYF_4,Yb~(3+)Er~(3+)的发射光谱与光敏剂MB的吸收光谱的匹配,在980nm激光激发下可以产生具有光动力治疗效果的单线态氧,并且激发光具有成像功能;并通过第三层丰富的介孔结构装载癌症治疗药物DOX;合成制备PEI-FA并通过静电力作用完成PEI-FA对载药粒子的包封;对三层核-壳-壳结构的UCNP@SiO_2(MB)@m SiO_2的表面进行改性修饰,使得通过PEI-FA包覆的介孔纳米粒子载药量增加。在功能性测试方面,本文仅对载药、p H响应控释效果以及光动疗方面做了研究性评估。通过改性前后的对比来说明载药性能的改进,通过不同的PEI-FA包封量的核-壳-壳结构纳米粒子在不同p H下的药物释放曲线来研究p H刺激响应的药物控释性能,并通过测定DPBF的紫外-可见吸光度的变化曲线来研究核-壳-壳结构纳米粒子的单线态氧产生能力。最终达到综合性评价核-壳-壳结构多功能载药纳米粒子UCNP@SiO_2(MB)@m SiO_2性能的结果以及潜在的生医应用价值。
[Abstract]:Traditional cancer treatment methods have the disadvantages of low curative effect, long course of treatment, high cost, high treatment risk and so on. Nowadays, researchers focus on developing new cancer treatment methods to overcome these disadvantages. Among the new methods are the targeted drug delivery technology for nanoparticles, which can be used for drug loading or photodynamic therapy. The new generation of drug loaded nanoparticles, which are in the research frontier, can integrate drug loading, external response control, specific targeting, biological imaging, in vivo diagnosis and photodynamic therapy to produce new multifunctional nanoparticles. The main purpose of this paper is to design a kind of nanoparticles with drug delivery, p H response, photodynamic therapy, specific target and biological imaging function, and to study the drug controlled release and photodynamic therapy performance of p-H stimulation response. In order to achieve the dual response of drug controlled release and single line oxygen phototherapy under the double stimulation of in vivo acidic environment and in vitro near-infrared light irradiation, the cocktail therapy can be realized. In the aspect of preparation, UCNP@SiO_2 (MB) @ m SiO_2 mesoporous nanoparticles with three-layer core-shell structure were synthesized and assembled by pyrolysis and sol-gel method. By matching the emission spectra of NaYF_4,Yb~ (3) Er~ (3) nanoparticles doped with lanthanide ions in the core with the absorption spectra of Guang Min (MB), a single line oxygen with photodynamic effect can be produced under the excitation of 980nm laser. And the excited light has imaging function, and the third layer of rich mesoporous structure is loaded with cancer treatment drug DOX; synthesis to prepare PEI-FA and complete the encapsulation of the drug carrier particles by PEI-FA through electrostatic action. The surface modification of UCNP@SiO_2 (MB) @ m SiO_2 with a three-layer core-shell structure resulted in an increase in the amount of drug loaded by mesoporous nanoparticles coated with PEI-FA. In the aspect of functional test, we only evaluated the controlled release effect of drug loaded, p H and photodynamic therapy. The improvement of drug loading performance was explained by the comparison before and after modification. The drug release properties of p-H stimulated response were studied by the drug release curves of core-shell structure nanoparticles with different PEI-FA entrapment amounts under different pH conditions. The single-line oxygen production ability of core-shell nanoparticles was studied by measuring the UV-Vis absorbance curve of DPBF. Finally, the results of comprehensive evaluation of the properties of core-shell multifunctional drug-loaded nanoparticles UCNP@SiO_2 (MB) @ m SiO_2 and the potential biomedical application value were achieved.
【学位授予单位】：哈尔滨工业大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：TB383.1;R943
，
本文编号：2285197
[Abstract]:Traditional cancer treatment methods have the disadvantages of low curative effect, long course of treatment, high cost, high treatment risk and so on. Nowadays, researchers focus on developing new cancer treatment methods to overcome these disadvantages. Among the new methods are the targeted drug delivery technology for nanoparticles, which can be used for drug loading or photodynamic therapy. The new generation of drug loaded nanoparticles, which are in the research frontier, can integrate drug loading, external response control, specific targeting, biological imaging, in vivo diagnosis and photodynamic therapy to produce new multifunctional nanoparticles. The main purpose of this paper is to design a kind of nanoparticles with drug delivery, p H response, photodynamic therapy, specific target and biological imaging function, and to study the drug controlled release and photodynamic therapy performance of p-H stimulation response. In order to achieve the dual response of drug controlled release and single line oxygen phototherapy under the double stimulation of in vivo acidic environment and in vitro near-infrared light irradiation, the cocktail therapy can be realized. In the aspect of preparation, UCNP@SiO_2 (MB) @ m SiO_2 mesoporous nanoparticles with three-layer core-shell structure were synthesized and assembled by pyrolysis and sol-gel method. By matching the emission spectra of NaYF_4,Yb~ (3) Er~ (3) nanoparticles doped with lanthanide ions in the core with the absorption spectra of Guang Min (MB), a single line oxygen with photodynamic effect can be produced under the excitation of 980nm laser. And the excited light has imaging function, and the third layer of rich mesoporous structure is loaded with cancer treatment drug DOX; synthesis to prepare PEI-FA and complete the encapsulation of the drug carrier particles by PEI-FA through electrostatic action. The surface modification of UCNP@SiO_2 (MB) @ m SiO_2 with a three-layer core-shell structure resulted in an increase in the amount of drug loaded by mesoporous nanoparticles coated with PEI-FA. In the aspect of functional test, we only evaluated the controlled release effect of drug loaded, p H and photodynamic therapy. The improvement of drug loading performance was explained by the comparison before and after modification. The drug release properties of p-H stimulated response were studied by the drug release curves of core-shell structure nanoparticles with different PEI-FA entrapment amounts under different pH conditions. The single-line oxygen production ability of core-shell nanoparticles was studied by measuring the UV-Vis absorbance curve of DPBF. Finally, the results of comprehensive evaluation of the properties of core-shell multifunctional drug-loaded nanoparticles UCNP@SiO_2 (MB) @ m SiO_2 and the potential biomedical application value were achieved.
【学位授予单位】：哈尔滨工业大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：TB383.1;R943
，
本文编号：2285197
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