FSHR结合肽修饰的纳米荧光探针的构建及其对卵巢癌转移灶的靶向示踪研究

Patients with advanced ovarian cancer have high mortality rate and poor prognosis. The key factor that determine survival time is the volume of residual disease after primary cytoreductive surgery. However, due to the complexity and wide range of the abdominal cavity, occult metastatic lesions may failed to be recognized and resected. In addition, adhesion and scar may be misjudged as cancerous tissue. Thus, accurate locating of metastatic ovarian cancer tissue is essential for optimal cytoreductive surgery. Ovarain cancer specifically expresses high level of FSHR. In our previous study, nano-particles targeting FSHR facilitated enrichment of chemotherapeutic agent in tumor tissues and improved tumor inhibition efficacy. This study intends 1) to search for an optimal FSHR binding poly-peptide using Phage Display Techniques to modify β-NaYF4:Yb, Er@NaYF4 upconversion nanophosphors, and as a result construct a novel fluorescent nonapartical probes targeting ovarian cancer tissue; 2) to investigate the sensitivity and tumor-specificity of the novel fluorescent probe for locating the ovarian cancer metastatic foci; 3) to test the toxicity of this probe for further clinical application.

晚期卵巢癌的预后差，死亡率高，初次肿瘤细胞减灭术后残留病灶的大小、数量是重要的预后因素。但由于卵巢癌在腹腔内的转移具有广泛性和隐匿性，肉眼和触感往往都难以辨识，在手术中易导致“漏杀”或者“误杀”，因此如何提高肿瘤细胞减灭术的准确性成了亟待解决的问题。卵泡刺激素受体（FSHR）在卵巢癌中特异性高表达，课题组前期构建的FSHR靶向性纳米载药系统能显著提高化疗药物抑瘤率。本项目拟用噬菌体展示技术筛选优化FSHR结合片段，用于修饰稀土上转换纳米材料β-NaYF4:Yb,Er@NaYF4核壳晶体结构，从而构建对卵巢癌具有主动靶向作用的新型纳米荧光探针。通过细胞实验和活体动物成像研究考察该新型荧光探针的灵敏度及其对卵巢癌病灶的特异性结合能力，评估该探针应用于卵巢癌术中成像、指导手术切除范围的可行性，同时初步研究该探针的生物毒性作用，为其临床应用提供依据。