| 摘要 | 第5-9页 |
| ABSTRACT | 第9-13页 |
| List of Abbreviations | 第14-20页 |
| Introduction | 第20-24页 |
| Background | 第20-21页 |
| Objectives of this research | 第21-22页 |
| Novelty of the work | 第22页 |
| References | 第22-24页 |
| Chapter 1 Literature Review | 第24-44页 |
| 1.1 Preface | 第24-25页 |
| 1.2 Allograft rejection mediating factors | 第25-26页 |
| 1.3 Biomimetic PLGA micro- and nanoscale antigen carriers | 第26-27页 |
| 1.4 Physical properties of PLGA particles | 第27-30页 |
| 1.4.1 Size-based tissue distribution | 第27-28页 |
| 1.4.2 Shape | 第28-29页 |
| 1.4.3 Physiochemical properties | 第29页 |
| 1.4.4 Dosage of immunoregulatory molecules | 第29-30页 |
| 1.5 Controlled release mechanisms/methods of control release | 第30-31页 |
| 1.5.1 Encapsulation | 第30-31页 |
| 1.5.2 Adsorption or co-coupling | 第31页 |
| 1.6 Immunoregulatory and immunomodulatory molecules | 第31-33页 |
| 1.7 Effects on overall immune functions | 第33-34页 |
| 1.8 Conclusion | 第34-35页 |
| 1.9 References | 第35-44页 |
| Chapter 2 Preparation and phenotypic characterization of killer PLGA nanoparticles | 第44-55页 |
| 2.1 Introduction | 第44-45页 |
| 2.2 Materials and Methods | 第45-49页 |
| 2.2.1 Reagents | 第45-46页 |
| 2.2.2 Instruments | 第46页 |
| 2.2.3 Preparation of PLGA-NPs and ICG-encapsulated PLGA-NPs | 第46页 |
| 2.2.4 Measurement of size and zeta potential | 第46-47页 |
| 2.2.5 Determination of shape and surface morphology | 第47页 |
| 2.2.6 Surface modification of PLGA-NPs | 第47页 |
| 2.2.7 Proteins coupling capability of PLGA-NPs | 第47-48页 |
| 2.2.8 Preparation of killer NPs, ICG-encapsulated killer NPs and PE-labeled killer NPs | 第48页 |
| 2.2.9 Phenotypic analysis of Killer NPs | 第48-49页 |
| 2.3 Results | 第49-51页 |
| 2.3.1 Characterization of PLGA-NPs | 第49页 |
| 2.3.2 Protein coupling capability of surface-modified PLGA-NPs | 第49-50页 |
| 2.3.3 Generation and phenotypic analysis of Killer NPs | 第50-51页 |
| 2.4 Discussion | 第51-52页 |
| 2.5 Conclusion | 第52页 |
| 2.6 References | 第52-55页 |
| Chapter 3 Killer NPs inhibit alloskin rejection and their in vivo mechanism | 第55-81页 |
| 3.1 Introduction | 第55-56页 |
| 3.2 Materials and Methods | 第56-62页 |
| 3.2.1 Reagents | 第56-57页 |
| 3.2.2 Mice and cell lines | 第57页 |
| 3.2.3 Instruments | 第57页 |
| 3.2.4 Skin Transplantation and treatment with Killer NPs | 第57-58页 |
| 3.2.5 Clinical evaluation of grafted bm1 mice | 第58页 |
| 3.2.6 Immunofluorescence and histopathological analyses of alloskin graft | 第58-59页 |
| 3.2.7 Detection of alloantigen-reactive CD8~+ T cells | 第59-60页 |
| 3.2.8 Detection of CD8~+ T cells apoptosis and activation | 第60页 |
| 3.2.9 Detection for the alloreactivity of CD8~+ T cells | 第60页 |
| 3.2.10 Detection of regulatory CD4~+ T cells | 第60-61页 |
| 3.2.11 In vivo and ex vivo near-infrared imaging | 第61页 |
| 3.2.12 Tissue distribution of killer NPs and contacts with immune cells | 第61-62页 |
| 3.2.13 Statistical analyses | 第62页 |
| 3.3 Results | 第62-75页 |
| 3.3.1 Killer NPs treatment markedly prolongs alloskin graft survival and reduces local allo-rejections | 第62-67页 |
| 3.3.2 Killer NPs treatment selectively depletes H-2K~b alloantigen-reactive CD8~+ T cells | 第67-68页 |
| 3.3.3 Killer NPs treatment facilitates the apoptosis of CD8~+ T cells, inhibits the activation and alloreactivity of T cells and induces regulatory T cells | 第68-71页 |
| 3.3.4 In vivo tracking and tissue distribution of killer NPs | 第71-73页 |
| 3.3.5 Co-localization of Killer NPs with CD8~+ T Cells in vivo | 第73-75页 |
| 3.4 Discussion | 第75-78页 |
| 3.5 Conclusion | 第78-79页 |
| 3.6 References | 第79-81页 |
| Chapter 4 Recipient overall immune function and organ toxicity after killer NPs treatment | 第81-100页 |
| 4.1 Introduction | 第81-82页 |
| 4.2 Materials and Methods | 第82-85页 |
| 4.2.1 Reagents | 第82页 |
| 4.2.2 Mice and cell lines | 第82-83页 |
| 4.2.3 Instruments | 第83页 |
| 4.2.4 T-cell proliferation in response to third-party spleen cells | 第83页 |
| 4.2.5 Enumeration of various immune cells in peripheral blood and spleen . | 第83-84页 |
| 4.2.6 Cytotoxicity assay of NK cells | 第84页 |
| 4.2.7 Evaluation of organ toxicity | 第84-85页 |
| 4.2.8 Tumor cells challenge | 第85页 |
| 4.2.9 Statistical analyses | 第85页 |
| 4.3 Results | 第85-96页 |
| 4.3.1 Killer NPs treatment does not affect the recipient overall immune function | 第85-89页 |
| 4.3.2 Treatment with killer NPs did not impair the host overall immune function and presented no apparent organ toxicity | 第89-96页 |
| 4.4 Discussion | 第96-98页 |
| 4.5 Conclusion | 第98页 |
| 4.6 References | 第98-100页 |
| Chapter 5 Summary of the Project and Future Work Plan | 第100-102页 |
| 5.1 Summary and conclusions | 第100-101页 |
| 5.2 Directions for future research | 第101-102页 |
| Appendix | 第102-104页 |
| First and co-first authored publications | 第102页 |
| Co-authored publications | 第102-103页 |
| Unpublished paper | 第103-104页 |
| Acknowledgement | 第104页 |
