SERS活性的脂质体@金银合金纳米复合材料的制备及药物可控释放

发布时间：2019-05-12 00:41

【摘要】：目前,如何实现药物的可控释放及对药物传递过程的追踪,已经成为生物纳米材料领域的热点问题。在本论文中,通过置换反应(GRR),制备了一种新型的脂质体@金银合金纳米复合材料,该纳米材料表现出从可见到近红外的表面等离子体共振特性。选取拉曼信号和荧光信号分子的蒽环类抗恶性肿瘤药物阿霉素作为目标药物,包载进脂质体@金银合金纳米复合材料,发现阿霉素药物分子的拉曼信号由于激光与等离子体的谐振耦合被增强,使其具有表面拉曼增强(SERS)活性,在药物传递过程中,可以通过追踪拉曼信号检测药物传递。当激光进行辐照,入射光光子激发金属纳米壳层电子,受激电子向外辐射能量,温度达到脂质体相转变温度后,内容药物阿霉素释放,即利用脂质体具有相转变温度及金属纳米壳层的光热转化效应,实现药物的可控释放。本论文研究的主要内容如下:(1)制备脂质体@金银合金纳米复合材料。首先,通过薄膜干燥结合超声波分散法制备了尺寸在79 nm的脂质体;柠檬酸三钠(Na3C6H5O7)作为保护剂,通过硼氢化钠(NaBH4)还原硝酸银(AgNO3)的方法制备尺寸在4 nm左右的银纳米粒子。随后,根据静电吸引相互作用,在脂质体表面包覆并生长一层致密银壳层。最后,通过银壳层与氯金酸(HAuCl_4)的氧化还原反应(GRR),制备出脂质体@金银合金纳米复合材料。使用扫描、透射电镜,粒度仪及紫外可见吸收光谱对复合纳米材料进行表征,随后研究加入金银体积比例对复合纳米材料的影响并研究了材料的光热特性,最后通过MTT实验讨论材料毒性,证明材料具有良好的生物相容性。(2)将蒽环类形抗癌药物阿霉素(DOX)包载入脂质体@金银合金纳米复合材料,并对复合材料的表面等离子体共振特性、表面增强拉曼特性以及荧光淬灭特性进行研究。金银合金纳米壳层可以吸收光能通过电磁场共振转移为热量,而脂质体作为一种具有相转变温度的特殊材料,当外界温度高于相转变温度时,磷脂分子从胶态变为液态,脂质体因结构改变而发生相转变,从而实现内容药物的释放。当用与脂质体@金银合金纳米材料表面等离子体共振峰位相匹配波长的激光照射材料时,会实现内容药物阿霉素的释放。通过光谱吸收强度、MTT实验、荧光猝灭及恢复现象,研究并证实了通过光热触发的可控性药物释放。
[Abstract]:At present, how to realize the controlled release of drugs and track the drug delivery process has become a hot issue in the field of biomaterials. In this thesis, a new type of liposomes @ gold-silver alloy nanocomposites was prepared by substitution reaction (GRR),. The nanomaterials exhibit surface plasmon resonance (SPR) properties from visible near infrared (NIR). Anthracycline anticancer drug doxorubicin, which is a Raman signal molecule and a fluorescent signal molecule, was selected as the target drug and included in liposomes @ gold and silver alloy nanocomposites. It was found that the Raman signal of doxorubicin molecule was enhanced by the resonance coupling between laser and plasma, which made it have surface Raman enhanced (SERS) activity. In the drug delivery process, the drug transfer could be detected by tracing the Raman signal. When the laser irradiation, the incident photons excite the metal nanoshell electrons, the stimulated electrons radiate the energy outward, and the temperature reaches the phase transition temperature of liposomes, and the content drug doxorubicin is released. That is to say, the controlled release of drugs can be realized by using the phase transition temperature of liposomes and the photothermal conversion effect of metal nanoshells. The main contents of this thesis are as follows: (1) Liposome @ au / Ag alloy nanocomposites were prepared. Firstly, liposomes with size of 79 nm were prepared by thin film drying and ultrasonic dispersion. Trisodium citrate (Na3C6H5O7) was used as protective agent to prepare silver nanoparticles with a size of about 4 nm by reducing silver nitrate (AgNO3) by sodium borohydroxide (NaBH4). Then, according to the electrostatic attraction interaction, a dense silver shell was deposited on the surface of the liposomes. Finally, liposomes @ gold-silver alloy nanocomposites were prepared by redox reaction of silver shell with chlorogold acid (HAuCl_4) (GRR),. The composite nano-materials were characterized by scanning electron microscopy, transmission electron microscopy, particle size analyzer and ultraviolet visible absorption spectrum. Then, the influence of the volume ratio of gold and silver on the composite nano-materials was studied, and the photothermal properties of the composites were also studied. Finally, the toxicity of the material was discussed by MTT test, and it was proved that the material had good biocompatibility. (2) the anthracycline anticancer drug doxorubicin (DOX) was loaded into liposomes @ gold-silver alloy nanocomposites. The surface plasmon resonance properties, surface enhanced Raman properties and fluorescence quenching properties of the composites were studied. Nano-shell of gold-silver alloy can absorb light energy to transfer heat through electromagnetic field resonance, while liposome is a special material with phase transition temperature. When the external temperature is higher than the phase transition temperature, the phospholipid molecule changes from colloid state to liquid state. The phase change of liposomes occurs due to structural changes, so as to realize the release of content drugs. When the laser irradiation wavelength matching the plasmon resonance peak position of liposomes @ gold and silver alloy nanomaterials is used, the release of doxorubicin can be realized. The controllable drug release triggered by photoheat was studied and confirmed by spectral absorption intensity, MTT experiment, fluorescence quenching and recovery.
【学位授予单位】：东北师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TB383.1;TB33;TQ460.1

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