论文总字数：19929字

摘 要

到目前为止，癌症始终威胁着人类的健康，每年都有数百万人死于各类癌症，对于抗癌药物的设计与开发从未停止，但由于早期设备简陋，对于微小肿瘤的监测和诊断很难取得较为准确的结果，为后续的治疗增加了更多的难度，另外，肿瘤侵袭转移的频繁发生也削弱了各类药物与手段的效用。为了对抗赢得与癌症的战争，迫切需要设计同时具有诊断功能又具有治疗功能的智能而强大的纳米药物，在癌症的早期重要阶段，为准确的诊断和治疗提供一个强力有效的多功能平台。

二茂铁及其衍生物和稀土上转换纳米材料所具有的优势使其进入人们的视线。关于二茂铁衍生物-上转换纳米复合物体系已有课题进行构筑，具有较好的抗肿瘤活性，二者之间产生有效地荧光能量共振转移，能够引发二茂铁衍生物在构筑的纳米复合物表面产生作用，促成羟基自由基和单线态氧的生成，利用光动力治疗手段致伤癌细胞。并在外包裹一层脂质体，利用脂质体在抗肿瘤方面的优势有效地改善了纳米复合物的溶解性和生物相容性，提高细胞对纳米复合物的融合吸收效率，从而更好地实现光动力治疗。本文制备了表面富含羧基的上转换纳米颗粒UCNPs-3MA，合成二茂铁环蕃香豆素（L1），并与铕配合，后通过简单的配位作用将Eu-L1负载到上转换纳米材料表面，构筑了二茂铁-铕-上转换纳米复合物体系。纳米复合物UCNPs-3MA-Eu-L1-Lipo光照组对AGS细胞的IC₅₀值为43.78 μg/mL，对MGC-803细胞的IC₅₀值为43.75 μg/mL，证明了在上转换纳米材料表面构筑二茂铁配合物壳层用于抗肿瘤研究的价值。

关键词：二茂铁 近红外光诱导 上纳米颗粒 光动力治疗

Abstract

So far, cancer has always threatened human health. Every year, millions of people die from various types of cancer. The design and development of anti-cancer drugs has never stopped, but due to the poor early equipment, the monitoring and diagnosis of small tumors It is difficult to obtain more accurate results, which adds more difficulty to the subsequent treatment. In addition, the frequent occurrence of tumor invasion and metastasis also weakens the effectiveness of various drugs and methods. In order to fight against the battle with cancer, there is an urgent need to design intelligent and powerful nano-medicines that have both diagnostic and therapeutic functions, and provide a powerful and effective multi-functional platform for accurate diagnosis and treatment in the early important stages of cancer.

The advantages of ferrocene and its derivatives and rare earth upconverting nanomaterial make it into people's sight. The loading of the ferrocene derivative-upconversion nanocomposite system has been subject to construction and has good antitumor activity. An effective fluorescence energy resonance transferring between the upconversion nanoparticles and the ferrocene derivative, triggers the ferrocene derivatives on the surface of the nanocomposite，generating hydroxyl radicals and singlet oxygen to realize photodynamic therapy. We use liposomes to encapsulate ferrocene derivative-upconversion nanocomposites, which effectively improve the solubility and biocompatibility of nanocomposites, improve the fusion absorption efficiency of cells to nanocomposites, and thus achieve better Photodynamic therapy. We prepared UCNPs-3MA, a carboxyl-rich upconvertion nanoparticle, synthesize ferrocene cyclo coumarin (L1) and coordination with europium, and loaded Eu-L1 onto the surface of the upconvertion nanoparticle by simple coordination to construct a ferrocene-Eu-upconversion nanocomposite system. The nanocomposite UCNPs-3MA-Eu-L1-Lipo irradiation group had an IC₅₀ value of 43.78 μg/mL for AGS cells and an IC₅₀ value of 43.75 μg/mL for MGC-803 cells, showing good antitumor activity. We explored the value of constructing a ferrocene complex shell on the surface of upconverting nanomaterials for antitumor research.

KEYWORDS: Ferrocene; NIR; UCNPs; PDT

目 录

摘 要 I

Abstract II

目 录 1

第一章 引言 1

1.1 上转换纳米材料 1

1.2 癌症诊断及治疗的研究进展 1

1.2.1 上纳米材料复合物对于癌症诊疗的应用 1

1.2.2 二茂铁衍生物对于癌症治疗的应用 2

1.2.3 胶质体在癌症治疗领域的应用 3

1.3 上转化纳米材料复合体构筑的研究意义 3

第二章 实验部分 6

2.1 实验材料、试剂、仪器 6

2.2 合成方法 9

2.2.1 NaYF4:Yb，Tm-3MA（UCNPs-3MA）上转换纳米颗粒的合成 9

2.2.2 Eu-L1配合物合成 9

2.2.3 UCNPs-3MA-Eu-L1复合物合成 10

2.2.4空白脂质体制备 10

2.2.5 UCNPs-3MA-Eu-L1-Lipo的合成（脂质体包裹UCNPs-3MA-Eu-L1） 10

2.3 实验方法 11

2.4 生物实验方法 11

第三章 实验结果与讨论 13

3.1 二茂铁-铕-上转换纳米复合物构筑 13

3.2 活性氧测试 15

3.3 近红外光诱导二茂铁-铕-上转换纳米复合物抗肿瘤活性 16

结语 20

参考文献 21

致谢 24

第一章 引言

1.1 上转换纳米材料

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