Nanostructured lipid carrier mediated co-Delivery of quantum dots and paclitaxel to tumour for cancer imaging and therapy:A multifunctional nanoparticle construct for theragnostic approach

摘要

肿瘤诊断治疗能够实现药物的体内可视化递送和肿瘤治疗的可视化监控，对于提高患者生活质量具有重要意义。纳米脂质载体(nanostructured lipid carriers，NLC)是一种独一无二的多功能的纳米递送系统。本课题的研究目标是构建一种共载量子点(CdTe/CdS/ZnS)和紫杉醇(paclitaxel，PTX)的NLC实现肿瘤的诊断与治疗的结合。该共载NLC选用甘油单硬脂酸酯、油酸、大豆卵磷脂作为基质材料，通过乳化蒸发和低温固化法制得。其粒径为115.93±1.61 nm，多分散系数为0.17±0.04，ζ电位为-0.22±0.03 mV，粒子为光滑圆整的球形，包封率为80.70±2.11％，载药量为4.68±0.04％，4℃下放置1个月仍保持稳定。体外PTX释放实验显示出比上市制剂taxol(R)更慢的释药速率。细胞摄取实验证实该制剂具有较好的入胞和诱导凋亡的能力。对肝癌细胞HEPG2的半数抑制浓度为1.05±0.58μM。体内抑瘤实验显示共载NLC与taxol(R)相比，具有更好的抑制荷瘤小鼠肿瘤生长(p＜0.05)的效果，抑制率达77.85％。药物组织分布实验证实共载NLC主要分布在肝、脾，其中在脾中的滞留时间最长。小鼠体内近红外成像实验显示共载NLC可特异性的靶向肿瘤部位，体现出良好的肿瘤诊断性能。以上实验证明我们制备的共载量子点(CdTe/CdS/ZnS)和PTX的NLC，作为一种静脉注射递送系统，可以很好的实现肿瘤的治疗和适时监控。

目录

声明

Abstract

摘要

Table of contents

List of tables

List of figures

List of acronyms

Thesis frame work

1．1 Statement

1．2 Literature review

1．3 Hypothesis

Chapter 2-Formulation

2．1 Introduction

2．2 Materials

2．3 Animals

2．5 Cell culture

2．6 Design

2．7．2 Results

2．7．3 Discussion

Chapter 3-Process of optimising the formulation

Chapter 4-PTX analytical method validation

4．1 Method and materials

4．2 Results

Chapter 5-Physicochemical characterisation of co-loaded NLC

5．1 Particle size，polydispersity and zeta potential measurements

5．1．1 Method and materials

5．1．2 Results

5．1．3 Discussion

5．2 Transmission electron microscopy (TEM)

5．2．1 Method and materials

5．2．2 Results

5．2．3 Discussion

5．3．1 Method and materials

5．3．2 Results

5．3．3 Discussion

5．4 Stability studies

5．4．1 Method and materials

5．4．3 Discussion

Chapter 6-In vitro studies

6．1 In vitro drug release study

6．1．1 Method and materials

6．1．2 Results

6．1．3 Discussion

6．2 In vitro cytotoxicity studies

6．2．1 Method and materials

6．2．2 Results

6．2．3 Discussion

6．3 Apoptosis assessment by Annexin V-FITC／propidiun iodide (PI) assay

6．3．1 Method and materials

6．3．2 Results

6．3．3 Discussion

6．4 In vitro cellular uptake study

6．4．1 Method and materials

6．4．2 Results

6．4．3 Discussion

Chapter 7-In-vivo and ex-vivo studies

7．1．1 Method and materials

7．1．2 Results

7．1．3 Discussion

7．2 In-vivo and Ex-vivo Fluorescence Optical Imaging abilities of the co-loaded NLC

7．2．1 Method and materials

7．2．2 Results

7．2．3 Discussion

7．3 Paclitaxel assay in major organs

7．3．1 Method and materials

7．3．2 Results

7．3．3 Discussion

7．4 Histopathological assessment by light microscopy

7．4．1 Method and materials

7．4．2 Results

7．4．3 Discussion

Chapter 8-Conclusion and future perspective

8．1 Conclusion

8．2 Future perspective

References

Chapter 10-Appendices

Dedications

Acknowledgements

List of publications

Published work