负载纳米金和抗癌药物的锂皂石—聚乙烯亚胺纳米平台的构建、功能化及其肿瘤诊疗的应用

发布时间：2018-01-17 12:30

本文关键词：负载纳米金和抗癌药物的锂皂石—聚乙烯亚胺纳米平台的构建、功能化及其肿瘤诊疗的应用　出处：《东华大学》2017年硕士论文　论文类型：学位论文

【摘要】：近年来,发展一种集成像与化疗为一体的多功能纳米平台应用于肿瘤的诊断和治疗是当前纳米医学领域的研究热点。在多种纳米载体中,无机纳米颗粒因其独特的结构和高药物负载能力在癌症治疗领域被广泛研究,但其表面不易于功能化修饰、稳定性较差等缺陷限制了在生物医学领域的进一步应用。因此,如果将具有大量官能团的高分子修饰到无机纳米材料表面构建一种杂化纳米颗粒,将有助于提高体系的稳定性、易于修饰靶向分子或成像试剂,为建立具有肿瘤成像与药物输送功能的诊疗一体化平台提供新的思路。在本课题中,以具有良好药物负载能力的锂皂石(LAP)和超支化聚乙烯亚胺(PEI)构建杂化纳米颗粒用于负载金纳米颗粒与抗癌药物阿霉素(DOX),并在表面修饰靶向分子透明质酸(HA),以实现靶向CD44受体高表达肿瘤的CT成像与化疗。首先,在锂皂石表面组装了末端为羧基的聚乳酸-聚乙二醇(PLA-PEG),再以1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐(EDC)活化羧基与聚乙烯亚胺(PEI)的氨基连接构建了LAP-PLA-PEG-PEI杂化纳米颗粒,并以此为模版合成了金纳米颗粒(Au NPs)、表面修饰透明质酸(HA),再负载抗癌药物阿霉素(DOX),制备了LAP-PLA-PEG-PEI-(Au~0)50-HA/DOX纳米复合物。合成的纳米复合物展现了良好的稳定性和优异的DOX上载率(91.0±1.8%),其中,DOX的缓释具有pH响应。体外的细胞毒性实验、流式细胞分析和激光共聚焦显微镜的结果显示所合成的纳米复合物能够对CD44受体高表达的癌细胞具有特异性传递和抑制。体内实验表明,LAP-PLA-PEG-PEI-(Au~0)50-HA/DOX复合纳米材料不仅能够抑制肿瘤的繁殖、减少阿霉素的毒副作用,而且可以作为肿瘤部位的靶向CT造影剂。因此,所合成的LAP-PLA-PEG-PEI-(Au~0)50-HA/DOX纳米复合物是一种对CD44过表达的肿瘤具有靶向成像和化疗功能的诊疗纳米平台。
[Abstract]:In recent years, the development of a multi-functional nano-platform integrated with chemotherapy for the diagnosis and treatment of cancer has become a research hotspot in the field of nanomedicine. Inorganic nanoparticles have been widely studied in the field of cancer treatment because of their unique structure and high drug loading ability, but their surfaces are not easily functionalized. Poor stability and other defects limit the further application in biomedical field. Therefore, if the polymer with a large number of functional groups is modified to the surface of inorganic nanomaterials, a hybrid nanoparticles can be constructed. It will help to improve the stability of the system, easy to modify target molecules or imaging reagents, and provide a new idea for the establishment of an integrated diagnosis and treatment platform with the function of tumor imaging and drug delivery. Hybrid nanoparticles were constructed from lithium-soap (LAP) and hyperbranched polyimide (PEI) to support gold nanoparticles and adriamycin (DOX). At the same time, we modify the target molecular hyaluronic acid to realize the CT imaging and chemotherapy of the target CD44 receptor overexpression tumor. Polylactic acid-poly (ethylene glycol) (PLA-PEG) was assembled on the surface of lithium saponite. Activation of carboxyl group and polyethylene imine (PEI) with 1-dimethylamino-propyl (1-dimethylamino-propyl) -3-ethylcarbodiimide (EDCC)). The LAP-PLA-PEG-PEI hybrid nanoparticles were constructed by Amino ligation. The gold nanoparticles, au NPsN, surface modified hyaluronic acid Ham, and adriamycin dox were synthesized on the template. LAP-PLA-PEG-PEI-(Au~0)50-HA/DOX nanocomposites were prepared. The synthesized nanocomposites showed good stability and excellent DOX upload rate (. (91.0 卤1.8). The slow release of DOX has pH response and cytotoxicity in vitro. The results of flow cytometry and laser confocal microscopy showed that the synthesized nanocomposites could specifically transfer and inhibit the expression of CD44 receptor in cancer cells. LAP-PLA-PEG-PEI-(Au~0)50-HA/DOX composite nanomaterials can not only inhibit the proliferation of tumors, but also reduce the toxicity and side effects of adriamycin. And can be used as a tumor site targeted CT contrast agent. The synthesized LAP-PLA-PEG-PEI-A0). The 50-HA / DOX nanocomposite is a nanoplatform for the diagnosis and treatment of CD44 overexpressed tumors with targeted imaging and chemotherapeutic functions.
【学位授予单位】：东华大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R979.1;TB383.1

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