新型功能化水溶性荧光量子点探针在乳腺癌靶向成像的应用研究

发布时间：2018-07-02 13:25

本文选题：乳腺癌 + 靶向成像　；参考：《吉林大学》2015年博士论文

【摘要】：乳腺癌已经成为当今女性发病最高的恶性肿瘤之一。这也要求对乳腺癌的生物学特性应有更加透彻的理解。目前雌激素受体（ER）和孕激素受体（PR）在乳腺癌的分子分型、治疗方案选取、预后的预测和疾病的监测方面都得到越来越多的重视。半导体纳米晶体量子点因其独特的光学和电子特性，近年被广泛应用于生物学方面研究中，尤其在在生物荧光成像方面表现出了突出的优势。本文通过将聚合物(PASP-Na-g-PEG-DDA)包覆修饰后形成的水溶性量子点，，连接ER和PR抗体后形成的具有靶向功能性的QD-ER和QD-PR探针。通过对体外乳腺癌细胞ER和PR的标记明确其特异性靶向性能力检测分析。随后通过对活体内肿瘤内的靶向标记成像能力也进行了验证，同时对探针的体内和体外的细胞毒性作用进行了分析。结果显示本研究制备的QD-ER和QD-PR探针，不仅显示出了出色的水溶性和稳定性，在体外细胞实验中既可以分别乳腺癌细胞的ER和PR特异性结合而显像，又能实现对同时细胞内ER和PR的同步标记。体内实验中QD-ER探针实现了对荷瘤小鼠的乳腺癌肿瘤位点靶向标记。体内和体外的毒性实验分析均未见明显毒性反应。这种新型的探针在乳腺肿瘤标志物检测，诊断和肿瘤的长时间观测方面显示出巨大的潜力，对于未来乳腺癌的生物学特性研究及早期诊断方面也将有着极佳的应用价值。
[Abstract]:Breast cancer has become one of the most common malignant tumors in women. This also requires a better understanding of the biological characteristics of breast cancer. At present, estrogen receptor (ER) and progesterone receptor (PR) have been paid more and more attention to the molecular classification of breast cancer, the selection of treatment regimen, prognosis prediction and disease monitoring. Due to their unique optical and electronic properties, semiconductor nanocrystalline quantum dots (QDs) have been widely used in biological research in recent years, especially in biological fluorescence imaging. In this paper, the QD-ER and QD-PR probes with targeted function were formed by encapsulating the modified polymer (PASP-Na-g-PEG-DDA) into water-soluble quantum dots (QDs), which were linked to ER and PR antibodies. The detection and analysis of specific targeting ability of breast cancer cell line ER and PR in vitro were carried out. Then the ability of target labeling imaging in vivo was also verified, and the cytotoxicity of the probe in vivo and in vitro was analyzed. The results showed that the QD-ER and QD-PR probes prepared in this study not only showed excellent water solubility and stability, but also could be combined with ER and PR of breast cancer cells in vitro. It can also realize the simultaneous labeling of ER and PR in cells. In vivo QD-ER probes have been used to target tumor sites in tumor-bearing mice. In vivo and in vitro toxicity test analysis showed no obvious toxic reaction. The new probe has great potential in the detection, diagnosis and long-term observation of breast tumor markers, and will be of great value in the study of biological characteristics and early diagnosis of breast cancer in the future.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R737.9

【共引文献】