pH响应星形聚合物单分子胶束用于抗癌药物递送和CT成像

发布时间：2018-03-24 23:15

本文选题：单分子胶束　切入点：金纳米粒子　出处：《华南理工大学》2016年硕士论文

【摘要】：“诊断及治疗复合纳米材料”可同时完成肿瘤靶向诊断及药物递送,实现诊疗一体化。本论文设计并合成了多功能星形聚合物单分子胶束,一步法原位还原制备稳定的金纳米粒子(GNPs),并负载抗癌药物阿霉素(DOX),用于CT诊断及药物递送。主要开展了以下研究工作:采用开环聚合(ROP)和电子转移活化剂再生-原子转移自由基聚合(ARGET ATRP)相结合的技术,合成两亲性星形嵌段共聚物β-环糊精-聚丙交酯-聚甲基丙烯酸二甲氨基乙酯-聚甲基丙烯酸2-乙基-2-恶唑啉酯[β-CD-(PLA-PDMAEMA-PEt OxMA)21]。在水溶液中,该聚合物形成以21臂β-CD为核、疏水性PLA为内层、还原性及pH敏感性PDMAEMA为中间层,亲水性PEtOxMA为外壳的结构稳定的单分子胶束。聚合物中PDMAEMA的叔胺基与金属离子形成配位,原位还原制备稳定的金纳米粒子,无需额外添加还原剂和有机溶剂。采用凝胶渗透色谱、核磁共振氢谱、红外光谱、动态光散射、透射电镜等多种方法和技术表征聚合物分子结构及单分子胶束性能;系统探讨了PDMAEMA嵌段长度、共聚物与HAuCl4的摩尔比、共聚物与HAuCl4溶液的浓度等对金纳米粒子大小、形貌的影响,以及金纳米粒子的稳定性。星形聚合物在水溶液中形成粒径不超过29 nm的单分子胶束。PDMAEMA嵌段越长、星形嵌段共聚物与HAuCl4的摩尔比越大、星形嵌段共聚物与HAuCl4的浓度越小,GNPs粒径越小、越均一。GNPs不仅能够在长达4个月时间内保持稳定,且不受pH变化的影响。以疏水性小分子药物DOX为模型药物,制备同时负载DOX和GNPs的复合纳米材料。该复合材料有明显的pH响应药物释放性能,在肿瘤部位弱酸性条件下,PDMAEMA嵌段响应pH变化,使内核溶胀,实现药物可控快速释放。同时,体内外CT成像结果显示,与传统小分子造影剂相比,GNPs具有更强的CT成像效果。因此,该复合材料具有肿瘤CT成像诊断及pH响应药物治疗的潜在应用价值。
[Abstract]:"Diagnostic and Therapeutic Composite Nanomaterials" can complete tumor targeting diagnosis and drug delivery at the same time and realize the integration of diagnosis and treatment. In this paper, a multifunctional star polymer monolayer micelle was designed and synthesized. The stable gold nanoparticles GNPs were prepared by one step in situ reduction and loaded with adriamycin doxan for CT diagnosis and drug delivery. The following research work was carried out: ring opening polymerization (ROP) and electron transfer activator regeneration. Atom transfer radical Polymerization combined with ARGET ATRP, The amphiphilic star block copolymer 尾 -cyclodextrin-poly (lactide) -dimethylaminoethyl methacrylate (DMA) -2-ethyl-2-oxazolinyl methacrylate (尾 -CD-PMAEMA-PEt OxMA)21) was synthesized. In aqueous solution, the polymer was formed with 21 arms 尾 -CD as the nucleus. Hydrophobic PLA is the inner layer, reductive and pH sensitive PDMAEMA is the intermediate layer, and hydrophilic PEtOxMA is the outer shell of monolayer micelles. The tertiary amine group of PDMAEMA in the polymer is coordinated with metal ions, and the stable gold nanoparticles are prepared by in-situ reduction. Gel permeation chromatography (GPC), nuclear magnetic resonance (NMR), IR, dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to characterize the molecular structure and micelle properties of the polymer. The effects of block length of PDMAEMA, molar ratio of copolymers to HAuCl4, concentration of copolymers and HAuCl4 solution on the size and morphology of gold nanoparticles were systematically discussed. And the stability of gold nanoparticles. The longer the monomolecular micelle. PDMAEMA block is formed in aqueous solution, the larger the molar ratio of star block copolymer to HAuCl4 is. The smaller the concentration of star block copolymers and HAuCl4, the smaller the particle size, the more homogeneous. GNPs can not only remain stable for up to 4 months, but also not be affected by the change of pH. The hydrophobic small molecular drug DOX is used as the model drug. The composite nanomaterials loaded with DOX and GNPs were prepared. The composite has obvious pH response to drug release, and PDMAEMA block responds to pH changes under the condition of weak acidity of tumor site, which results in swelling of the core and the controllable and rapid release of the drug. In vivo and in vitro CT imaging results show that GNPs have stronger CT imaging effect than traditional small molecular contrast agents. Therefore, the composite has potential application value in tumor CT imaging diagnosis and pH response drug therapy.
【学位授予单位】：华南理工大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：O631;TQ460.1

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