宫颈癌是最常见的妇科恶性肿瘤之一，克服顺铂（Cisplatin）耐药是宫颈癌化疗中的难题。研究表明，外泌体（exosome）由于较低的免疫原性及良好的归巢能力被认为是最理想的化疗药物纳米载体之一。因此，本项目拟在本课题组前期构建的质粒转染（慢病毒体系）的基础上开发一种膜上表达TRAIL蛋白的exosome，并在该exosome中装载Bcl-2-siRNA和Cisplatin，形成TRAIL-exosome@Bcl-2-siRNA&Cisplatin共载纳米系统。通过体外实验验证该纳米系统能有效提高Cisplatin对耐药的宫颈癌细胞SiHa/CDDP的肿瘤抑制效果。同时，验证该纳米系统在免疫正常小鼠中的生物相容性，并在本课题组已经成功构建的SiHa/CDDP宫颈癌皮下移植瘤和原位瘤的动物模型中验证该纳米系统对体内肿瘤的靶向性及肿瘤抑制效果，为有效治疗Cisplatin耐药宫颈癌提供新思路。

Cervical cancer is one of the most common gynecologic malignancies. Cisplatin resistance is a difficult problem to overcome in the chemotherapy of cervical cancer. Researches showed that exosome was considered to be one of the most ideal chemotherapy drug nanocarriers attributed to its low immunogenicity and good homing ability. Therefore, this project intends to develop an exosome with its membrane expressing TRAIL protein on the basis of plasmid transfection by lentiviral systems which we have constructed, and then to load Bcl-2-siRNA and Cisplatin into the exosome, finally forming a TRAIL-exosome@Bcl-2-siRNA&Cisplatin co-loaded nanosystem. We will verify through vitro experiment that the nanosystem can effectively improve the sensitivity of drug-resistant cervical cancer cell line (SiHa/CDDP) to Cisplatin, and enhance Cisplatin inhibitory effect on tumor. Furthermore, we will also verify this nanosystem's biological compatibility in immune normal mice, and its in vivo tumor targeting and tumor inhibitory effect in the cervical SiHa/CDDP carcinoma subcutaneous transplantation tumor and in situ tumor animal model which we have already successfully constructed, and provide new ideas for the effective treatment of cisplatin resistant cervical cancer.