摘 要

Abstract 5

1 绪论 6

1.1 癌症的治疗现状 6

1.2 纳米诊疗法 7

1.3 基于金属有机骨架材料的纳米诊疗法 8

2 研究内容 12

3实验部分 13

3.1主要实验药品与仪器 13

3.2 PCN-224@DOX和PCN-224@（DOX ICG）的制备 14

3.3 PCN-224@DOX和PCN-224@（DOX ICG ）的表征 166

4结果与讨论 17

4.1 TPPCOOMe和H₂TCPP的表征 17

4.2 PCN-224的表征 199

4.3 PCN-224@DOX的表征 20

4.4 PCN-224@（DOX ICG）的表征 21

4.5 结论 21

参考文献 23

致谢 26

摘 要

癌症是威胁人类生命的最大杀手之一。全球纳米技术的迅猛发展给肿瘤治疗带来一场全新的变革，其中纳米诊疗法作为一种新型癌症治疗方式显示出巨大的潜力。纳米诊疗学将癌症的治疗和成像组合在一个单一的纳米平台，即构建癌症的诊疗一体化纳米平台。在纳米材料中，金属有机骨架材料是一类具有可调控的化学结构和组成、有序的结晶三维骨架、极高的比表面积和孔隙度的“明星”材料。在本课题的研究中，我们构建了一种可同时实现光动力治疗、化疗和荧光成像的多功能的nMOFs（纳米金属有机骨架材料）的纳米诊疗一体化平台，主要研究内容和结论如下所示：

1. 研究内容：首先用苯甲酸、H₂TCPP（5，10，15，20-四（4-苯甲酸）卟啉）、八水合氯氧化锆合成具有光动力治疗功能的nMOFs——PCN-224，用透射电镜、扫描电镜、X射线粉末衍射、紫外可见分光光度计等进行一系列表征；然后用浸泡法使其负载抗癌药盐酸阿霉素（DOX），制得纳米载药粒子PCN-224@DOX，随后对其进行后续的表征；随后进一步尝试用浸泡法使其同时负载盐酸阿霉素和荧光成像试剂吲哚菁绿（ICG），制得多功能纳米载药粒子PCN-224@（DOX ICG），用紫外可见分光光度计对其进行表征。
2. 研究结论：荧光光谱表明成功制备了纳米载药粒子PCN@DOX，这证明PCN-224的光动力治疗与化疗协同的可行性，同时DOX的载药量相对于已有研究来说非常高，高达64%。紫外吸收光谱显示成功得到多功能纳米载药粒子PCN@（DOX ICG），进一步证明PCN-224的光动力治疗与化疗、荧光成像整合到单一平台的可行性。至此，我们已经初步得到集光动力治疗、化疗和荧光成像于一体的多功能纳米诊疗平台PCN-224@（DOX ICG）。

关键词：多功能nMOFs，药物输送，诊疗一体化，癌症

Abstract

Cancer is one of the deadliest killers that threaten human life. The rapid development of global nanotechnology brings a new revolution for tumor treatment,including nanotherapy which has shown marvelous potential as a neotype of cancer treatment.Nanotherapy is to integrate the therapeutic and imaging agents in one nanomaterial platform,namely,to construct a theranostic nanoplatform. Among nanomaterials, the metal organic framework material is a kind of "star" material with adjustable chemical structure and composition, ordered crystalline three-dimensional structure, high specific surface area and porosity.In our study, we constructed a multi-functional nMOFs(nanoscale metal-organic frameworks) theranostic nanoplatform that simultaneously enables photodynamic therapy, chemotherapy, and fluorescence imaging.The main research contents and conclusions are as follows:

In this paper, Firstly, nMOFs PCN-224 with photodynamic therapy is synthesized by using benzoic acid,Tetrakis(4-carboxyphenyl)porphyrin (TCPP) and zirconium oxychloride octahydrate.A series of characterization is carried out by transmission electron microscopy,Scanning electron microscopy,X-ray powder diffraction and UV-visible spectrophotometer and so on.And then PCN-224 is loaded with anticancer drug DOX(doxorubicin hydrochloride) by immersion method to prepare drug-loaded nanoparticles PCN-224@DOX, followed by subsequent characterization. Then we also via the immersion method simultaneously load DOX and fluorescent imaging reagent ICG（Indocyanine Green）to prepare PCN@(DOX ICG),which is characterized by UV-Vis spectrophotometer.

The results show that the drug-loading nanoparticles PCN@DOX are successfully constructed , which proves the feasibility of PCN-224 photodynamic therapy and chemotherapy synergies, while DOX drug loading relative to the existing study is very high ,up to 64%.The results of the following studies show that PCN@(DOX ICG) nanoparticles are successfully obtained,which further demonstrated the feasibility of PCN-224 photodynamic therapy in combination with chemotherapy and fluorescence imaging. At this point, We have initially obtained PCN-224@(DOX ICG), a multifunctional nanoscale theranostic platform for photodynamic therapy, chemotherapy and fluorescence imaging.

Key words：multi-functional nMOFs,drug delivery, theranostics,cancer

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