AIE功能化介孔硅纳米材料的制备及其在生物医药中的应用

发布时间：2018-08-20 08:56

【摘要】：随着癌症诊疗技术的不断发展,荧光成像导向的可控药物释放体系可在提高化疗效果的同时减少治疗过程中产生的副作用。基于其比表面积大、孔径均一且可控等独特的结构特征及优异的生物相容性,介孔氧化硅纳米粒子可作为理想的药物运输载体。有机荧光分子功能化的无机材料结合了二者的优势,在荧光成像导向的药物控释体系领域具有潜在应用。然而,当传统的具有聚集诱导荧光淬灭(ACQ)性质的有机染料掺杂进无机材料中时,其荧光可能会淬灭,从而影响成像结果。与ACQ体系相比,聚集诱导发光(AIE)生色团因其分子内旋转受限可在固态发射较强荧光,为无机有机荧光杂化材料的发展提供了新的可能。AIE分子被引入无机材料后,其分子内运动被无机基质所限,所得杂化材料可表现出典型的AIE现象。在此基础上,我们制备了AIE功能化的介孔硅纳米材料,并探索了其在细胞成像及药物释放等生物医药领域中的应用。本论文所取得主要结果如下:利用“表面活性剂导向的碱刻蚀法”合成了规则的中空介孔二氧化硅纳米粒子(HMSNs),随后将含有四苯乙烯核的有机分子BTPE通过后嫁接的方式连接到HMSNs上,得到AIE功能化的中空介孔二氧化硅纳米材料(FMSNs)。所得材料具有大空腔和介孔壳层结构,并在紫外光激发下发出强烈蓝色荧光。尤为重要的是,该种材料生物相容性好,药物装载量大,并且具有pH响应的药物释放性质。该材料可作为荧光探针并有效的应用于细胞内成像,展现了其在成像导向的癌症治疗中的应用。将超小硫化铜(CuS)纳米晶修饰在AIE功能化的介孔氧化硅纳米粒子表面并用于细胞成像及协同的化学/光热癌症治疗。所制备的纳米复合材料生物相容性好,在紫外激发下可发射强烈蓝色荧光,可用作细胞内成像的荧光探针。除此之外,粒子表面附着的CuS纳米晶在808 nm近红外光下可以产生明显的热效应,达到有效的光热抗癌治疗效果。与此同时,盐酸阿霉素(DOX)通过静电吸附被装载进MSNs,并且其释放速率可被NIR照射后导致的热效应显著增加,达到化学药物/光热治疗的协同效果。
[Abstract]:With the development of cancer diagnosis and treatment technology, the controlled drug release system guided by fluorescence imaging can not only improve the effect of chemotherapy but also reduce the side effects. Because of its large specific surface area, uniform pore size and controllable structure and excellent biocompatibility, mesoporous silica nanoparticles can be used as ideal carrier for drug transport. Organic fluorescent molecular functionalized inorganic materials combine the advantages of the two materials and have potential applications in the field of fluorescence imaging oriented drug controlled release system. However, when conventional organic dyes with the properties of agglomeration induced fluorescence quenching (ACQ) are doped into inorganic materials, their fluorescence may be quenched, thus affecting the imaging results. Compared with ACQ system, agglomeration induced luminescent (AIE) chromophore can emit strong fluorescence in solid state due to its limited intramolecular rotation, which provides a new possibility for the development of inorganic organic fluorescent hybrid materials. The intramolecular motion is limited by the inorganic matrix, and the hybrid materials can exhibit typical AIE phenomenon. On this basis, we have prepared AIE functionalized mesoporous silicon nanomaterials and explored their applications in biomedical applications such as cell imaging and drug release. The main results obtained in this thesis are as follows: the regular hollow mesoporous silica nanoparticles (HMSNs), were synthesized by "Surfactant oriented Alkali etching method" and then the organic molecule BTPE containing tetrastyrene nucleus was grafted. To connect to the HMSNs, AIE functionalized hollow mesoporous silica nanomaterials (FMSNs). The obtained materials have large cavity and mesoporous shell structure and emit strong blue fluorescence excited by ultraviolet light. It is particularly important that the material has good biocompatibility, large drug loading and pH response drug release properties. The material can be used as a fluorescent probe and can be effectively used in intracellular imaging, showing its application in image-oriented cancer therapy. Ultrasmall copper sulfide (CuS) nanocrystals were modified on the surface of AIE functionalized mesoporous silica nanoparticles and used for cell imaging and synergistic chemical / photothermal cancer therapy. The nanocomposites have good biocompatibility and can emit strong blue fluorescence under UV excitation, and can be used as fluorescence probes for intracellular imaging. In addition, the CuS nanocrystalline attached to the particle surface can produce obvious thermal effect under 808 nm near-infrared light, which can achieve an effective photothermal anticancer effect. At the same time, doxorubicin hydrochloride (DOX) was loaded into MSNs by electrostatic adsorption, and the release rate of doxorubicin hydrochloride was significantly increased after NIR irradiation, and the synergistic effect of chemotherapeutic / photothermal therapy was achieved.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TB383.1;TQ460.1

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