论文总字数：30720字

摘 要

目前，绝大多数的造影剂的半衰期都比较的短，更重要的是对肿瘤诊断不具备特异性，甚至会产生一些不良的反应或副作用，这对肿瘤的诊断是非常不利的。因此，需要一种能够在外加磁场下准确定位在病变部位，且能作为抗癌药物（如阿霉素）靶向载体的造影剂。本文采用复合工艺，先通过共沉淀法、高温乙酰丙酮铁分解法以及购买Fe₃O₄分散液制备得到磁性Fe₃O₄纳米粒子，将他们分别与SiO₂前驱体复合，得到三种磁性Fe₃O₄/SiO₂气凝胶颗粒，然后负载抗癌药物阿霉素。并对其微球的饱和磁化强度、BET比表面积、阿霉素药物的载药率以及体外释放率进行测试分析。

对三种磁性Fe₃O₄ /SiO₂颗粒进行表征测试后发现，乙酰丙酮铁高温分解法制备的Fe₃O₄粒子制备的复合颗粒，它的饱和磁化强度为1.25A·m²·kg^-1，而购买的Fe₃O₄分散液所制备的复合颗粒饱和磁化强度为20A·m²·kg^-1，并且在H=0时它们的矫顽力以及剩磁都几乎为0，两种粒子都具有良好的超顺磁性。共沉淀法制备得到的Fe₃O₄/SiO₂复合颗粒的比表面积为853.2533m²/g，高温分解法制备得到的Fe₃O₄/SiO₂复合颗粒的比表面积为769.4886，磁性Fe₃O₄分散液复合的Fe₃O₄/SiO₂复合颗粒，它的比表面积为401.5395m²/g。与抗肿瘤药物阿霉素复合之后，三种Fe₃O₄/SiO₂颗粒对阿霉素药物的装载率分别为1.77%、4.58%、4.76%。表面修饰NH₂后再装载包裹蛋白的Fe₃O₄/SiO₂-NH₂-蛋白对阿霉素的负载率分别为3.85%、4.76%、5.30%。 可以得到改性后的Fe₃O₄/SiO₂-NH₂-蛋白的负载率较未改性的Fe₃O₄/SiO₂颗粒要高一些。经过阿霉素药物释放实验后，共沉淀、高温分解法以及Fe₃O₄分散液复合的Fe₃O₄/SiO₂- NH₂-蛋白@DOX，其释放要比Fe₃O₄/SiO₂@DOX的缓慢一些，效果不是很显著。需要进一步的完善实验方案来进行验证。

关键词： 磁性 Fe₃O₄/SiO₂气凝胶 靶向载体 造影剂

Preparation and properties of magnetic Fe₃O₄/SiO₂ aerogel-borne doxorubicin contrast agent

Abstract

At present, most contrast agents have a relatively short half-life, and more importantly, they are not specific for tumor diagnosis, and even produce some adverse reactions or side effects, which is very unfavorable for tumor diagnosis. Therefore, there is a need for a contrast agent that can be accurately positioned at the lesion under an external magnetic field and can be used as a targeting carrier for anticancer drugs (such as doxorubicin). In this paper, a composite process is used. First, magnetic Fe₃O₄ nanoparticles are prepared by co-precipitation, high-temperature acetylacetone iron decomposition, and the purchase of Fe₃O₄ dispersion. They are combined with SiO₂ precursors to obtain three magnetic Fe₃O₄/SiO₂ aerogel particles. Then loaded with anticancer drug doxorubicin. The saturation magnetization, BET specific surface area, doxorubicin drug loading rate and in vitro release rate of the microspheres were tested and analyzed.

After characterizing and testing three kinds of magnetic Fe₃O₄/SiO₂ particles, it was found that the saturation magnetization of Fe₃O₄ particles prepared by pyrolysis of iron acetylacetonate and composite particles prepared from the purchased Fe₃O₄ dispersion were 1.25A·m²·kg^-1,20A·m²·kg^-1, and when the external magnetic field is removed, their coercive force and remanence are almost zero, both particles have good superparamagnetism. The specific surface area of the Fe₃O₄/SiO₂ composite particles prepared by the coprecipitation method is 853.2533m²/g, the specific surface area of the Fe₃O₄/SiO₂ composite particles prepared by the pyrolysis method is 769.4886 m²/g, and the Fe₃O₄/SiO₂ composite particles composited by the magnetic Fe3O4 dispersion The specific surface area is 401.5395 m²/g. After being combined with the anti-tumor drug doxorubicin, the loading rates of the three Fe₃O₄/SiO₂ particles on the doxorubicin drug were 1.77%, 4.58%, and 4.76%. After the surface was modified with NH₂, the loading rate of the protein-coated Fe₃O₄/SiO₂-NH₂-protein to adriamycin was 3.85%, 4.76%, and 5.30%. It can be obtained that the modified Fe₃O₄/SiO₂-NH₂-protein loading rate is higher than the unmodified Fe₃O₄/SiO₂ particles. After the doxorubicin drug release experiment, the Fe₃O₄/SiO₂-NH₂-protein@DOX co-precipitated, pyrolyzed, and Fe₃O₄ dispersion compound released more slowly than Fe₃O₄/SiO₂@DOX, and the effect was not very significant. Need to further improve the experimental program to verify.

Key Words: Magnetic; Fe₃O₄/SiO₂ aerogel; Targeting vector; Contrast agent

目 录

摘 要 II

Abstract II

第一章 绪论 1

1.1引言 1

1.2磁性靶向药物载体的研究进展 1

1.2.1 磁性靶向药物系统简介 1

1.2.2 磁性药物载体的常见类型 1

1.2.3 磁性药物载体在肿瘤诊断上的应用 2

1.3 SiO₂气凝胶 3

1.3.1 研究现状 3

1.3.2 制备及干燥方法 3

1.3.3 生物医学应用 4

1.4 磁性Fe₃O₄/SiO₂气凝胶载阿霉素造影剂 4

1.4.1 磁性Fe₃O₄纳米颗粒 4

1.4.2 磁性Fe₃O₄/SiO₂复合气凝胶的制备 5

1.4.3 Fe₃O₄/SiO₂气凝胶载阿霉素造影剂性能 5

1.5本论文的研究意义和内容 6

1.5.1研究意义 6

1.5.2研究内容 6

第二章 磁性Fe₃O₄/SiO₂气凝胶颗粒的制备及其表征 8

2.1引言 8

2.2实验原料极其设备 8

2.2.1原料 8

2.2.2实验仪器 9

2.3纳米Fe₃O₄/SiO₂复合气凝胶微球的制备 9

2.3.1磁性纳米Fe₃O₄的制备 9

2.3.2 SiO₂前躯体的制备 10

2.3.3磁性纳米Fe₃O₄/SiO₂复合气凝胶颗粒的制备 10

2.4测试表征方法 11

2.4.1 XRD测试分析 11

2.4.2 透射电镜测试分析 12

2.4.3 透射电镜能谱测试分析 13

2.4.4红外光谱测试分析 14

2.4.5振动样品磁场计测试分析 15

2.4.6比表面积测试分析 16

第三章 气凝胶载阿霉素复合微球的制备及载药性能 18

3.1气凝胶载阿霉素复合微球的制备 18

3.1.1原料 18

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