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Developing Nanomedicine Approaches:Design,Synthesis,and Eval

发布时间:2021-07-09 14:04
  光学活性纳米剂作为一种新型的纳米医学材料,在癌症光疗法和成像方面展示出巨大的应用前景。然而,单一疗法存在副作用较多以及治疗效果有限等问题,具有高抗癌效率的联合疗法成为目前研究的趋势。最近,精准治疗结合了引导成像的多模式协同治疗优势,相比于单独成像或普通治疗,精准治疗对于治疗癌症展现出更严格的诊断和更高的治疗比率。因此,在本论文中,我们创新性的设计和合成了多功能光学活性纳米剂,用来解决单一疗法存在的问题,并通过癌症诊断和治疗的协同作用达到更好的治疗效果。本论文包括如下三个部分:第一部分,我们合成了一种具有光热/光动力协同治疗(PTT/PDT)效应的光学活性纳米剂。在这里,我们用普鲁士蓝(Prussian blue,PB)来修饰具有氧缺陷的氧化钼纳米颗粒(MoO3-x NPs),并通过简单的一锅法来控制材料的尺寸和形貌。所制备的PB-MoO3-x NPs具有均匀的粒径(~90纳米)和较好的水分散性,在第一生物窗口中表现出强烈的光学吸收,这是由于具有氧缺陷的MoO3-x颗粒中的等离子共振引起的。更重要的是,PB-MoO3-x NPs不仅具有~63.... 

【文章来源】:中国科学技术大学安徽省 211工程院校 985工程院校

【文章页数】:111 页

【学位级别】:博士

【文章目录】:
摘要
Abstract
Abbreviations
Chapter 1 Introduction
    1.1 Introduction
        1.1.1 Background and Motivation
    1.2 Cancer Monotherapy
        1.2.1 Photothermal Therapy (PTT)
        1.2.2 Photodynamic Therapy (PDT)
        1.2.3 Gene Therapy (GT)
        1.2.4 Current Limitations in Monotherapy
    1.3 Combination Therapy
        1.3.1 Photothermal/Photodynamic Combination Therapy
        1.3.2 Photothermal/Gene Combination Therapy
        1.3.3 Imaging Guide Therapy
    1.4 Future Challenges and Perspectives
    1.5 Objectives
    1.6 Thesis Organization
    1.7 References
Chapter 2 Plasmonic MoO_(3-x) Nanoparticles Incorporated in Prussian blue FrameworksExhibit Highly Efficient Dual Photothermal/Photodynamic Therapy
    2.1 Introduction
    2.2 Experimental Details
        2.2.1 Chemicals and Reagents
        2.2.2 Characterization
        2.2.3 Synthesis Of PB-MoO_(3-x)NCs
        2.2.4 Photothermal Effect Measurements
        2.2.5 Detection of ROS under NIR Light Irradiation
        2.2.6 Cell Lines and Cell Culture
        2.2.7 CCK-8 Cell Viability Assay
        2.2.8 Synergistic Photothermal and Photodynamic Killing Effect
        2.2.9 Apoptosis Assay
        2.2.10 Western Blotting
        2.2.11 Animals and Tumor Models
        2.2.12 TUNEL Assay
    2.3 Results and Discussion
        2.3.1 Synthesis and Characterization of PB-MoO_(3-x) Nanocomposites
        2.3.2 Photothermal Conversion Performance of PB-MoO_(3-x)NCs
        2.3.3 ROS Generation by PB-MoO_(3-x) NCs
        2.3.4 In vitro Phototherapeutic Studies
        2.3.5 In vivo Phototherapeutic Studies
    2.4 Summary
    2.5 References
Chapter 3 Polydopamine Coated PB-MnO_2 Nanoparticles as an Oxygen GeneratorNanosystem for Imaging-Guided Single-NIR-Laser Triggered SynergisticPhotodynamic/Photothermal Therapy
    3.1 Introduction
    3.2 Experimental Details
        3.2.1 Chemicals and Materials
        3.2.2 Characterization
        3.2.3 Synthesis of PB, PB-MnO_2 Nanoparticles
        3.2.4 Synthesis of PB-MnO_2@PDA Nanoparticles
        3.2.5 Ce6 Conjugated to PB-MnO_2@PDA Nanoparticles
        3.2.6 Photothermal Effect Measurements
        3.2.7 Oxygen Production of PB Nanomaterials
        3.2.8 T1-MR Imaging Performance
        3.2.9 Cell Lines and Cell Culture
        3.2.10 Detection of ROS
        3.2.11 Cell Uptake Assay
        3.2.12 In vitro Cytotoxicity Assay
        3.2.13 In vitro Hypoxia Relief
        3.2.14 Apoptosis Assay
        3.2.15 Tumour Model
        3.2.16 In vivo Tumor Therapeutic Efficacy Study
        3.2.17 Statistical Analysis
    3.3 Results and Discussion
        3.3.1 Design, Synthesis, and Photochemical Properties of Synthesized PB Nanomaterials
        3.3.2 Photothermal Performance of PB Nanomaterials
        3.3.3 Oxygen Production by PB Nanomaterials
        3.3.4 T1-MRI Properties of PB Nanomaterials
        3.3.5 Extracellular ROS Generation by PB Nanomaterials
    3.4 In vitro Phototherapeutic Efficacy
        3.4.1 Intracellular ROS Generation
        3.4.2 Hypoxia Relief Effect
        3.4.3 Cell Uptake and Cytotoxicity
    3.5 In vivo Phototherapeutic Efficacy
    3.6 Summary
    3.7 References
Chapter 4 Hematite@PEDOT Core-Shell Nanoparticles Exhibit Efficient PhotothermalGene Synergistic Therapy of Breast Cancer
    4.1 Introduction
    4.2 Experimental Details
        4.2.1 Chemicals and Reagents
        4.2.2 Characterization
        4.2.3 Synthesis of Fe_2O_3, Fe_2O_3@PEDOT Core-Shell Nanoparticles
        4.2.4 Synthesis of Fe_2O_3@PEDOT-siRNA Nanocomplexes
        4.2.5 Measurements of Photothermal Performance
        4.2.6 Cell Lines and Cell Culture
        4.2.7 Cell Viability Assay
    4.3. Results and Discussion
        4.3.1 Synthesis and Characterization of Fe_2O_3@PEDOT Nanoparticles
        4.3.2 Optical Properties of the Core-Shell Fe_2O_3@PEDOT NPs
        4.3.3 Photothermal Performance of Fe_2O_3@PEDOT Core-Shell NPs
        4.3.4 In vitro Photothermal Performance of Fe_2O_3@PEDOT Core-Shell NPs
        4.3.5 In Vitro Synergistic Photothermal-Gene Therapy of Fe_2O_3@PEDOT-siRNANanocomplexes
    4.4 Summary
    4.5 References
Acknowledgments
List of Publications



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