Fe3O4-葡聚糖-抗人子宫肉瘤干细胞样细胞功能性单克隆抗体磁性纳米粒的制备及其靶向治疗作用的研究

项目名称： Fe3O4-葡聚糖-抗人子宫肉瘤干细胞样细胞功能性单克隆抗体磁性纳米粒的制备及其靶向治疗作用的研究

项目编号： No.81472433

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 蔡净亭

作者单位： 中南大学

项目金额： 70万元

中文摘要： 子宫肉瘤是女性生殖道的恶性肿瘤，尽管它的发病率只占子宫恶性肿瘤的2-4%， 但是超过了子宫恶性肿瘤死亡原因的25%。这很大程度上与子宫肉瘤强大的侵袭转移能力、对放、化疗反应差以及极易复发有关。因此，开发新的针对子宫肉瘤的治疗方案是必需的。本课题组前期已证实人子宫肉瘤干细胞样细胞（HUSSLCs）在子宫肉瘤生长、转移和化疗耐药中发挥着关键性作用，而目前尚缺乏直接针对肿瘤干细胞（TSCs）的治疗手段。因此, 针对子宫肉瘤干细胞的靶向治疗有望克服临床上现有治疗手段的缺陷, 改善子宫肉瘤患者的预后。据此，本课题拟利用前期分离的HUSSLCs，建立大容量功能性单克隆抗体库， 筛选、鉴定能识别并且对HUSSLCs具有抑制作用的功能性单抗，并以前期研制的Fe3O4-葡聚糖纳米颗粒为载体，从体内及体外两个方面探讨功能性单抗对HUSSLCs的靶向抑制作用，以期为子宫肉瘤的靶向治疗提供有应用价值的候选治疗剂。

中文关键词： C23_子宫体肿瘤；肿瘤干细胞；功能性单克隆抗体；靶向治疗；磁性纳米载体

英文摘要： Uterine sarcoma is a malignant tumor of female genitalia, representing only 2% to 4% of all uterus malignant tumors,however, it accounts for over 25% of uterus malignant tumors death. It attributes largely to the strong invasive ability, the poor response to radiotherapy and chemotherapy and the easy to recurrence. Therefor,it is ergent and necessary to find new effective treatments for uterine sarcoma. In earlier work, we have confirmed that human uterine sarcoma stem -like cells（HUSSLCs）play a crucial role in tumor growth, metastasis and chemoresistance. However, we lack effective treatment methods against tumor stem cells (TSCs). Therefore, targeted therapy for uterine sarcoma stem cells is expected to overcome the defects of the existing clinical treatment and improve the prognosis of patients. So in this study we try to establish the high-capacity functional monoclonal antibody (mAb) library screening using HUSSLCs which are separated and purified early, and isolate and identify the functional mAbs which can distinguish and inhibit HUSSLCs. Subsequently, using pre-developed Fe3O4-dextran nanoparticle carrier, we explore the inhibitory effects of functional mAbs on HUSSLCs from both in vivo and in vitro. According to this study, we expect we can find out some valuable candidate therapeutic agents for the targeted treatment of uterine sarcoma.

英文关键词： uterine sarcoma;tumor stem cell;functional McAb;targeted therapy;magnetic nanoparticles