功能化纳米给药系统在抗癌治疗中的应用
发布时间：2023-04-28 16:54
恶性肿瘤是严重威胁人类健康的多发病之一,目前主要的临床治疗手段是化疗。但传统小分子药物往往肿瘤特异性不高,加上药物本身的理化性质缺陷如水难溶,药效受到限制。纳米递药系统可以有效提高药物的靶向性,在递送疏水性药物中发挥独特的优势,相关研究取得了很大的进展。无机纳米药物传递平台(具有金属核心的NDDPs)已成为靶向抗癌治疗中有前途的载药载体。在各种无机纳米粒子中,介孔二氧化硅纳米粒子(MSNs)和金纳米粒子(Au NPs)具有巨大的抗癌治疗潜力。首先,本课题开发了一种既具有CD44靶向性又具有线粒体靶向性的新型酶响应型多级靶向抗癌药物传递系统。将线粒体靶向化合物三苯基膦(TPP)接枝到MSN表面,而后进行阿霉素(DOX)的装载,最后用肿瘤靶向分子透明质酸(HA)封端,形成最终的纳米体系(MSN-DPH)。体外实验结果表明,肿瘤细胞通过CD44受体介导的内吞作用优先吸收MSN-DPH。此外,由于TPP的线粒体靶向能力,MSN-DPH主要聚集在线粒体中。透明质酸酶对透明质酸的降解促进了癌细胞中DOX的释放。因此,MSN-DPH能有效地杀死癌细胞,同时对正常细胞的细胞毒性要低得多。接下来,本论文...
【文章页数】：98 页
【学位级别】：博士
【文章目录】：
ACKNOWLEDGEMENTS
DEDICATION
LIST OF ABBREVIATIONS
ABSTRACT
摘要
Chapter 1:General Introduction and Review of Literature
1.1 Introduction
1.2 Doxorubicin(DOX):A Potential Anti-Cancer Drug
1.3 Inorganic NDDPs Implicated in Anti-Cancer Therapy
1.3.1 MSNs based NDDPs Implicated in Anti-Cancer Therapy
1.3.2 AuNPs Based NDDPs Implicated in Anti-Cancer Therapy
1.4 Glycosaminoglycans(GAGs)and Their Implications in Anti-Cancer Therapy
1.5 Significance of Reserch
1.6 Objectives
Chapter 2:Enzyme Responsive Mesoporous Silica Nanoparticles for Tumor Cells and Mitochondria Multistage-Targeted Drug Delivery
2.1 Introduction
2.2 Materials and Methods
2.2.1 Materials
2.2.2 Characterizations
2.2.3 Synthesis and Ammonization of MSNs(MSN-NH2)
2.2.4 Synthesis of Triphenylphosphine Propionic Acid and Preparation of MSN-NH2-TPP
2.2.5 Preparation of DOX Loaded MSNs(MSN-DPH)
2.2.6 Release of DOX from MSN-DOX and MSN-DPH
2.2.7 Cellular Uptake and Intracellular Localization of MSN-DPH
2.2.8 In Vitro Cytotoxicity of MSN-DPH
2.2.9 Statistical Analysis
2.3 Results and Discussion
2.3.1 Preparation and Characterization Analysis of MSN-DPH
2.3.2 FTIR Analysis of Synthesised MSN-DPH
2.3.3 HAase-responsive DOX Release from MSN-DPH
2.3.4 Multistage Targeting Capability of MSN-DPH
2.3.5 In Vitro Antitumor Effect of MSN-DPH
Chapter 3:Study of Prepration and Characterization of Au@MSNs and Glycosaminoglycans(GAGs)Modified Au@MSNs Nanoparticles
3.1 Introduction
3.2 Materials and Methods
3.2.1 Reagents
3.2.2 Instruments Used
3.2.3 Preparation of Au@MSNs
3.2.4 Modification of Au@MSNs to Prepare Au@MSNs-SH
3.2.5 Modification of Hyaluronic Acid,Heparin Sodium and Heparan Sulfate
3.2.6 Measuring the Amount of Thiol Grafted on Surface GAGs
3.2.7 Characterization of Modified GAGs
3.3 Results and Discussion
3.3.1 Characterization of Au@MSNs
3.3.2 Particle Size of Au@MSNs
3.3.3 Characterization of Au@MSNs-SH
3.3.4 The Amount of Grafted Thiol Group on Surface of GAGs
3.3.5 FTIR Analysis of Thiolated GAGs
Chapter 4: Study of Preparation, Drug Release Profiles and Anti-Cancer Activity of Au@MSNs@GAGs Nanoparticles
4.1 Introduction
4.2 Materials and Methods
4.2.1 Reagents
4.2.2 Instruments Used
4.2.3 Plotting the Standard Curve of DOX
4.2.4 Au@MSNs-SH Drug Loading
4.2.5 Bonding between Au@MSNs-SH and GAG-SH
4.2.6 Drug Release from Au@MSNs@GAGs
4.2.7 Photothermal Effect of Au@MSNs@GAGs
4.2.8 In Vitro Cytotoxicity of Analysis of Au@MSNs@GAGs on HepG2 cells
4.2.9 In Vitro Cytotoxicity of Analysis of Au@MSNs@GAGs on Cos7 cells
4.2.10 Synergistic Effects of Au@MSNs@GAGs and Photothermal Therapy
4.2.11 Cellular Uptake and Intracellular Localization of Au@MSNs@GAGs
4.3 Results and Discussion
4.3.1 Drug Loading and Entrapment Efficiency of Au@MSNs-SH
4.3.2 Characterization of Au@MSNs@GAGs
4.3.3 Particle Size Measurements
4.3.4 Transmission Electron Microscopy Analysis
4.3.5 Drug Release Profiles from Au@MSNs@GAGs
4.3.6 Photothermal Effect of Au@MSNs@GAGs
4.3.7 Cytotoxic Assay of Au@MSNs@GAGs
4.3.8 Synergistic Effect of Au@MSNs@GAGs and Photothermal Therapy
4.3.9 Cellular Uptake of Au@MSNs@GAG by HepG2 Cells
Chapter 5:General Conclusion,Key innovations and Future Research
5.1 General Conclusions
5.2 Key innovations
5.3 Future Research
Bibliography
List of Publications
本文编号：3804095
【文章页数】：98 页
【学位级别】：博士
【文章目录】：
ACKNOWLEDGEMENTS
DEDICATION
LIST OF ABBREVIATIONS
ABSTRACT
摘要
Chapter 1:General Introduction and Review of Literature
1.1 Introduction
1.2 Doxorubicin(DOX):A Potential Anti-Cancer Drug
1.3 Inorganic NDDPs Implicated in Anti-Cancer Therapy
1.3.1 MSNs based NDDPs Implicated in Anti-Cancer Therapy
1.3.2 AuNPs Based NDDPs Implicated in Anti-Cancer Therapy
1.4 Glycosaminoglycans(GAGs)and Their Implications in Anti-Cancer Therapy
1.5 Significance of Reserch
1.6 Objectives
Chapter 2:Enzyme Responsive Mesoporous Silica Nanoparticles for Tumor Cells and Mitochondria Multistage-Targeted Drug Delivery
2.1 Introduction
2.2 Materials and Methods
2.2.1 Materials
2.2.2 Characterizations
2.2.3 Synthesis and Ammonization of MSNs(MSN-NH2)
2.2.4 Synthesis of Triphenylphosphine Propionic Acid and Preparation of MSN-NH2-TPP
2.2.5 Preparation of DOX Loaded MSNs(MSN-DPH)
2.2.6 Release of DOX from MSN-DOX and MSN-DPH
2.2.7 Cellular Uptake and Intracellular Localization of MSN-DPH
2.2.8 In Vitro Cytotoxicity of MSN-DPH
2.2.9 Statistical Analysis
2.3 Results and Discussion
2.3.1 Preparation and Characterization Analysis of MSN-DPH
2.3.2 FTIR Analysis of Synthesised MSN-DPH
2.3.3 HAase-responsive DOX Release from MSN-DPH
2.3.4 Multistage Targeting Capability of MSN-DPH
2.3.5 In Vitro Antitumor Effect of MSN-DPH
Chapter 3:Study of Prepration and Characterization of Au@MSNs and Glycosaminoglycans(GAGs)Modified Au@MSNs Nanoparticles
3.1 Introduction
3.2 Materials and Methods
3.2.1 Reagents
3.2.2 Instruments Used
3.2.3 Preparation of Au@MSNs
3.2.4 Modification of Au@MSNs to Prepare Au@MSNs-SH
3.2.5 Modification of Hyaluronic Acid,Heparin Sodium and Heparan Sulfate
3.2.6 Measuring the Amount of Thiol Grafted on Surface GAGs
3.2.7 Characterization of Modified GAGs
3.3 Results and Discussion
3.3.1 Characterization of Au@MSNs
3.3.2 Particle Size of Au@MSNs
3.3.3 Characterization of Au@MSNs-SH
3.3.4 The Amount of Grafted Thiol Group on Surface of GAGs
3.3.5 FTIR Analysis of Thiolated GAGs
Chapter 4: Study of Preparation, Drug Release Profiles and Anti-Cancer Activity of Au@MSNs@GAGs Nanoparticles
4.1 Introduction
4.2 Materials and Methods
4.2.1 Reagents
4.2.2 Instruments Used
4.2.3 Plotting the Standard Curve of DOX
4.2.4 Au@MSNs-SH Drug Loading
4.2.5 Bonding between Au@MSNs-SH and GAG-SH
4.2.6 Drug Release from Au@MSNs@GAGs
4.2.7 Photothermal Effect of Au@MSNs@GAGs
4.2.8 In Vitro Cytotoxicity of Analysis of Au@MSNs@GAGs on HepG2 cells
4.2.9 In Vitro Cytotoxicity of Analysis of Au@MSNs@GAGs on Cos7 cells
4.2.10 Synergistic Effects of Au@MSNs@GAGs and Photothermal Therapy
4.2.11 Cellular Uptake and Intracellular Localization of Au@MSNs@GAGs
4.3 Results and Discussion
4.3.1 Drug Loading and Entrapment Efficiency of Au@MSNs-SH
4.3.2 Characterization of Au@MSNs@GAGs
4.3.3 Particle Size Measurements
4.3.4 Transmission Electron Microscopy Analysis
4.3.5 Drug Release Profiles from Au@MSNs@GAGs
4.3.6 Photothermal Effect of Au@MSNs@GAGs
4.3.7 Cytotoxic Assay of Au@MSNs@GAGs
4.3.8 Synergistic Effect of Au@MSNs@GAGs and Photothermal Therapy
4.3.9 Cellular Uptake of Au@MSNs@GAG by HepG2 Cells
Chapter 5:General Conclusion,Key innovations and Future Research
5.1 General Conclusions
5.2 Key innovations
5.3 Future Research
Bibliography
List of Publications
本文编号：3804095
本文链接：https://www.wllwen.com/yixuelunwen/yiyaoxuelunwen/3804095.html
最近更新
教材专著
