T1/T2双模MRI纳米探针在乳腺癌靶向分子诊疗中的基础与应用研究

项目名称： T1/T2双模MRI纳米探针在乳腺癌靶向分子诊疗中的基础与应用研究

项目编号： No.81501459

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 刘桂锋

作者单位： 吉林大学

项目金额： 18万元

中文摘要： 乳腺癌是女性最常见的恶性肿瘤，严重威胁女性生命健康。当前，乳腺癌异质性导致其肿瘤生物学行为复杂，尤其是无ER，PR，HER2受体的三阴性乳腺癌更因缺乏特异性受体而相对诊疗困难。因此研究新的三阴性乳腺癌靶向诊疗探针具有重要意义。MRI作为一种先进的影像诊断手段，在乳腺癌的诊断中起着重大作用，然而常规MRI对乳腺癌的成像缺乏特异性，且对某些类型的组织缺乏足够的对比度，常需注射对比剂实现更佳的成像效果，但目前单一T1或者T2成像对比剂仍然难以满足复杂的肿瘤诊断需求。基于此，本课题以新型T1/T2双增强金-铂-氧化铁纳米颗粒为平台，以前期工作中证明在三阴乳腺癌高表达的CXCR4为靶点，通过简易的化学方法制备以CXCR4靶向的T1/T2双增强的MRI纳米分子探针，并进一步负载miR-22作为治疗药物，评价其在乳腺癌中的诊断及治疗的基础和效果， 从而为乳腺癌的诊断、定位及个性化治疗等提供一个新的方法。

中文关键词： 核磁共振成像；乳腺癌；动态增强；诊疗探针；纳米颗粒

英文摘要： Breast cancer is the most common malignancy among women and severely threatens women’s health. Breast cancer diagnosis is of great difficult because of its complex biological behaviors. Diagnosis and treatment is even more difficult in a specific subtype named triple negative breast cancer (TNBC), which lacks prominent tumor markers including estrogen receptors (ER-), progesterone receptors (PR-), and HER2 (HER2-). Hence, developing molecular theranostics that could specifically target TNBC is of great value and significance. Magnetic resonance imaging (MRI) plays important rule in facilitating breast cancer diagnosis, however, conventional MRI suffers low tumor detection specificity and sometimes lacks of enough tissue contrast. Currently, T1 or T2 signal enhancing contrasts are often utilized to obtain better MR images. But single enhancement of either T1 or T2 signal still could not fulfill the diagnostic requirements. Therefore, we aim to synthesize a Gd loaded Au-Pt-Iron oxide nanoparticle (named as DB-HNT) which could simultaneously enhance both T1 and T2 signal. We will also conjugate the DB-HNT with peptides which can bind with the previously identified TNBC marker CXCR4, to establish a dual signal enhanced molecular probe for breast cancer diagnosis. Moreover, we will incorporate miR-22, a small non-coding RNA which plays important roles in preventing cancer metastasis, into our CXCR4 targeted DB-HNT to develop a TNBC theranostic agent named as CM-DB-HNT. Overall, we expect that our research will provide a new method and technique for breast cancer diagnosis, localization as well as personalized treatment.

英文关键词： Magnetic Resonance Imaging;Breast Cancer;Dynamic Enhancement;Theranostic Probe;Nanoparticle