介入分子影像引导下的乳腺癌精准诊疗

发布时间：2019-04-18 13:20

【摘要】：乳腺癌是全世界女性最常见的恶性肿瘤,随着诊断技术的进步,乳腺癌早期诊断率的提高,乳腺癌生存率得到很大提高。尽管有综合诊疗方案,但是III-IV期乳腺癌死亡率高于50%。因此,对于乳腺癌来说,乳腺癌早期发现和治疗水平的提高是降低死亡率重要决定因素。但乳腺癌是一个异质性疾病,无论在组织学形态、肿瘤细胞免疫表型、基因表达及突变还是对治疗的反应上都存在很大的差异。针对乳腺癌不同个体的个体化诊断和精准医疗具有极大的前景。本论文用介入及分子影像的手段,探讨了在介入及分子影像引导下实现乳腺癌精准诊断和治疗一体化。本论文研究的主要内容及结论如下：第一部分本项研究首次发明用介入引导射频加热方法局部治疗乳腺癌的新技术。本研究中介入传递球囊导管的导丝通道和外部的射频发射装置相连接,同时实现介入导引和射频加热。本研究利用介入本身微创及能直接到达病变部位,在病变部位局部注射化疗药后用射频器械局部加热,通过进入乳腺癌细胞化疗药增多,使乳腺癌细胞凋亡增加等机制来增强化疗疗效。而且局部用药避免了全身用药引起的重要器官毒性及肿瘤组织内药物浓度过低等问题。第二部分在这项研究中,先合成二氧化硅介孔纳米材料,在二氧化硅介孔中通过原位的溶胶凝胶方法生成CaF2:Yb3+/Tm3+纳米晶,这种合成发光CaF2:Yb3+/Tm3+功能化二氧化硅介孔纳米材料方法尚未被报道过,而且容易实现。用简便方法合成的一系列不同尺寸(65nm、170nm、290nm)新的上转换发光的介孔二氧化硅纳米粒子(MSN)。此外,中孔通道内剩余的空间可以用作包载药物。该设计提供了先进的药物输送的的手段并利用上转换纳米发光材料对细胞损伤小和光穿透更深的优点使得细胞内或活体药物输送监测成为可能。进一步的试验显示材料本身低毒或无毒,载药后显示良好的杀乳腺癌作用,尤其是65 nm的纳米颗粒。
[Abstract]:Breast cancer is the most common malignant tumor in women all over the world. With the progress of diagnosis technology, the early diagnosis rate of breast cancer has been improved, and the survival rate of breast cancer has been greatly improved. Despite the availability of comprehensive treatment, III-IV breast cancer mortality rate is higher than 50%. Therefore, for breast cancer, early detection and treatment of breast cancer is an important determinant of reduced mortality. However, breast cancer is a heterogeneous disease, there are significant differences in histological morphology, tumor cell immunophenotype, gene expression and mutation, and response to treatment. Individualized diagnosis and accurate medical treatment for different individuals of breast cancer have great prospects. In this paper, we discuss the integration of accurate diagnosis and treatment of breast cancer guided by interventional and molecular imaging. The main contents and conclusions of this thesis are as follows: in the first part, a new technique for the local treatment of breast cancer with interventional-guided radio frequency heating was first invented. In this study, the wire guide channel of the interventional transmission balloon catheter is connected with the external RF transmitter, and the interventional guidance and radio frequency heating are realized at the same time. In this study, the intervention itself was minimally invasive and could reach the lesion site directly. After local injection of chemotherapeutic drugs into the lesion site, radio frequency devices were used for local heating, and the number of chemotherapeutic drugs was increased by entering the breast cancer cells. To increase the apoptosis of breast cancer cells and other mechanisms to enhance the efficacy of chemotherapy. Moreover, local administration avoids the important organ toxicity caused by systemic administration and the low drug concentration in tumor tissue. In the second part of this study, silica mesoporous nano-materials were firstly synthesized and CaF2:Yb3 / Tm3 nanocrystals were synthesized by in-situ sol-gel method in silica mesoporous media. The synthesis of luminescent CaF2:Yb3 / Tm3 functionalized silica mesoporous nanomaterials has not been reported and is easy to be realized. A series of novel up-conversion light emitting mesoporous silica nanoparticles (MSN). With different sizes (65 nm, 170 nm, 290 nm) were synthesized by a simple method. In addition, the remaining space in the mesoporous channel can be used as a drug pack. The design provides an advanced means of drug delivery and makes it possible to monitor drug delivery within cells or in vivo by using up-conversion nanoluminescent materials with the advantages of less damage to cells and deeper light penetration. Further tests showed that the material itself was low toxic or non-toxic, and showed a good anti-breast cancer effect after drug loading, especially 65 nm nanoparticles.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R737.9

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