發(fā)布時(shí)間：2021-07-09 14:04

　　光學(xué)活性納米劑作為一種新型的納米醫(yī)學(xué)材料,在癌癥光療法和成像方面展示出巨大的應(yīng)用前景。然而,單一療法存在副作用較多以及治療效果有限等問題,具有高抗癌效率的聯(lián)合療法成為目前研究的趨勢(shì)。最近,精準(zhǔn)治療結(jié)合了引導(dǎo)成像的多模式協(xié)同治療優(yōu)勢(shì),相比于單獨(dú)成像或普通治療,精準(zhǔn)治療對(duì)于治療癌癥展現(xiàn)出更嚴(yán)格的診斷和更高的治療比率。因此,在本論文中,我們創(chuàng)新性的設(shè)計(jì)和合成了多功能光學(xué)活性納米劑,用來解決單一療法存在的問題,并通過癌癥診斷和治療的協(xié)同作用達(dá)到更好的治療效果。本論文包括如下三個(gè)部分:第一部分,我們合成了一種具有光熱/光動(dòng)力協(xié)同治療（PTT/PDT）效應(yīng)的光學(xué)活性納米劑。在這里,我們用普魯士藍(lán)（Prussian blue,PB）來修飾具有氧缺陷的氧化鉬納米顆粒(MoO_3-x NPs),并通過簡(jiǎn)單的一鍋法來控制材料的尺寸和形貌。所制備的PB-MoO₃-x NPs具有均勻的粒徑（～90納米）和較好的水分散性,在第一生物窗口中表現(xiàn)出強(qiáng)烈的光學(xué)吸收,這是由于具有氧缺陷的MoO3-x顆粒中的等離子共振引起的。更重要的是,PB-MoO3-x NPs不僅具有～63.... 

【文章來源】：中國(guó)科學(xué)技術(shù)大學(xué)安徽省 211工程院校 985工程院校

【文章頁數(shù)】：111 頁

【學(xué)位級(jí)別】：博士

【文章目錄】：
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
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