| Abstract | 第5-7页 |
| Abbreviations | 第8-14页 |
| Chapter 1 Introduction | 第14-24页 |
| 1.1. Applications of nanotechnology in medicine | 第14-20页 |
| 1.1.1. Drug delivery | 第15-18页 |
| 1.1.2. Nanotechnology for therapeutic applications | 第18-20页 |
| 1.1.3. Application of nanotechnology in diagnosis | 第20页 |
| 1.2. Potential of nanomedicine to overcome multidrug resistance in cancer | 第20-24页 |
| 1.2.1. Multidrug resistance | 第20-22页 |
| 1.2.2. Strategies to overcome MDR with nanomedicines in cancer | 第22-24页 |
| Chapter 2 Experiment material and Methods | 第24-32页 |
| 2.1. Cell lines,compounds and reagents | 第24-27页 |
| 2.1.1. Cell lines | 第24页 |
| 2.1.2. Compounds | 第24-25页 |
| 2.1.3. Reagents | 第25-27页 |
| 2.2. Instruments and apparatuses | 第27-28页 |
| 2.3. Experimental Methods | 第28-30页 |
| 2.3.1. Freezing cells | 第28-29页 |
| 2.3.2. Thawing cells | 第29页 |
| 2.3.3. Passaging cells | 第29-30页 |
| 2.4. Determination of cell viability | 第30-32页 |
| Chapter 3 Toxicological screening of the nanocarriers loaded 5-fluorouracil forcancer treatment | 第32-37页 |
| 3.1. Aim to study | 第32页 |
| 3.2. Materials and methods | 第32-33页 |
| 3.2.1.Materials | 第32页 |
| 3.2.2. Cell lines and cell culture | 第32页 |
| 3.2.3. MTT assay | 第32-33页 |
| 3.3.Results | 第33-36页 |
| 3.3.1. Cytotoxicity effect of blank nano-based products | 第33-34页 |
| 3.3.2. Time course and dose-dependent response of cancer cells to nanopartilces | 第34-36页 |
| 3.4. Conclusion | 第36-37页 |
| Chapter 4 Collagen—based multicellular tumor spheroid model for evaluationof the efficiency of nanoparticle drug delivery | 第37-46页 |
| 4.1. Aim to study | 第37页 |
| 4.2. Materials and Methods | 第37-39页 |
| 4.2.1. Meterials | 第37-38页 |
| 4.2.2. Cells and cell culture | 第38页 |
| 4.2.3. Multicellular spheroid culture | 第38页 |
| 4.2.4. Cytotoxicity assay | 第38-39页 |
| 4.2.5. Confocal microscopy and estimation of nanoparticle penetration | 第39页 |
| 4.2.6. Statistics | 第39页 |
| 4.3. Results | 第39-44页 |
| 4.3.1. Morphology of tumor cells in 2-D vs 3-D | 第39-40页 |
| 4.3.2. Optimization of cell seeding density | 第40-41页 |
| 4.3.3. Validation of established 3-D tumor models | 第41-44页 |
| 4.4. Conclusion | 第44-46页 |
| Chapter 5 Overcoming Multidrug Resistance in 2-D and 3-D Culture Modelsby Controlled Drug Chitosan-Graft Poly(Caprolactone)-Based Nanoparticles | 第46-64页 |
| 5.1. Aim to study | 第46-47页 |
| 5.2. Materials and Methods | 第47-50页 |
| 5.2.1. Materials | 第47页 |
| 5.2.2. Synthesis of CS-g-PCL copolymer NPs and incorporation of 5-FU into NPs | 第47-48页 |
| 5.2.3. Drug release assay | 第48页 |
| 5.2.4. Cell lines and cell cultures | 第48-49页 |
| 5.2.5. Cytotoxicity evaluation and in vitro growth inhibition assay | 第49页 |
| 5.2.6. Intracellular concentration of 5-FU | 第49页 |
| 5.2.7. Rhodamine 123 accumulation assay | 第49-50页 |
| 5.2.8. Cells apoptosis assay | 第50页 |
| 5.2.9. Statistical analysis | 第50页 |
| 5.3. Results | 第50-61页 |
| 5.3.1. Preparation and characterization of 5-FU NPs | 第50-51页 |
| 5.3.2. Growth characteristics of HCT116 and HCT8 cell lines in 3-D collagen scaffold | 第51-52页 |
| 5.3.3. Cytotoxicity in monolayer and 3-D cultures | 第52-55页 |
| 5.3.4. Intracellular concentration of 5-FU in cells in monolayer and in 3-D scaffolds | 第55-57页 |
| 5.3.5. Influence of nonloaded NPs on Rh123 dye efflux in MDR cells | 第57-58页 |
| 5.3.6. Apoptosis of cells in 3-D collagen scaffold induced by 5-FU/NPs | 第58-61页 |
| 5.4. Discussion | 第61-62页 |
| 5.5. Conclussion | 第62-64页 |
| Chapter 6 Investigation of antitumor efficiency of novel sustained and targeted5-fluorouracil nanoparticles | 第64-84页 |
| 6.1. Aim to study | 第64-66页 |
| 6.2. Materials and Methods | 第66-69页 |
| 6.2.1. Materials | 第66页 |
| 6.2.2. Synthesis of FA-conjugated nanoparticles | 第66页 |
| 6.2.3. Prepare and characterization of FA-conjugated 5-FU-loaded nanoparticles | 第66-67页 |
| 6.2.4. In vitro drug-release studies | 第67页 |
| 6.2.5. Hemolysis assay | 第67页 |
| 6.2.6. Cell lines and culture conditions | 第67页 |
| 6.2.7. Intracellular drug concentration assay | 第67-68页 |
| 6.2.8. In vitro cytotoxicity assay | 第68页 |
| 6.2.9. Apoptosis analysis | 第68-69页 |
| 6.2.10. In vivo tumor inhibition and histopathological study | 第69页 |
| 6.2.11. Statistical analysis | 第69页 |
| 6.3. Results | 第69-82页 |
| 6.3.1. Characterization of 5-FU-loaded FA-conjugated nanoparticles | 第69-71页 |
| 6.3.2. In vitro effects of FA/5-FU/NP on colorectal cancer cell lines | 第71-78页 |
| 6.3.3. In vivo anti-tumor efficacy of FA conjugated 5-FU loaded nanoparticles | 第78-82页 |
| 6.4. Discussion and conclusion | 第82-84页 |
| Chapter 7 Conclusion and perspectives | 第84-86页 |
| References | 第86-101页 |
| Acknowledgements | 第101-102页 |
| Awards and Honors | 第102页 |
| Publications | 第102-103页 |
