共载药物及基因治疗已成为肿瘤治疗研究热点。为进一步增强共载体系抗肿瘤效应及减轻毒性，针对肿瘤高表达叶酸受体、高浓度谷胱甘肽和酸性环境特点，本项目构建叶酸分子靶向组氨酸及树枝状聚赖氨酸修饰的具有谷胱甘肽/pH双重敏感的星型聚合物(FA-CD-NH-NH=CH-SS-PLLD-His)，其共载多烯紫杉醇及TFPI-2质粒的纳米复合物对鼻咽癌进行靶向双重敏感综合治疗，通过HPLC、活体成像、RT-PCR及Western-blot法、MTT法、流式细胞术、Matrigel侵袭实验、HE染色、免疫组化、TUNEL法等，研究该复合物理化特征、基因转染效率、对鼻咽癌的靶向性、在荷鼻咽癌裸鼠体内分布、转染前后叶酸受体阳性的HNE-1细胞TFPI-2 mRNA和蛋白表达、对体内器官组织的毒性以及对NPC的体内外抑制效应。探索分子靶向双重敏感共载药物及基因治疗NPC的可行性和有效性，为临床应用提供实验依据。

Co-delivery of chemotherapy drugs and gene has become research hotspots for the tumor treatment nowadays. In order to enhance its anti-tumor effect and reduce the toxicity furtherly, in view of higher expression of folate receptor(FR)、higher GSH concentration and acid environment in tumor tissue, folic acid molecular targeted star type polymer modified by histidine(His) and poly(L-lysine) dendron(PLLD) with GSH/pH dual-sensitivity(FA-CD-NH-NH=CH-SS-PLLD-His) will be constructed to co-delivery Docetaxel(DOC) and TFPI-2 expressing plasmid, and FA-CD-NH-NH=CH-SS-PLLD-His/DOC/TFPI-2 nanocomposites will be used for targeted dual-sensitive therapy for nasopharyngeal carcinoma(NPC) in this project. Furthermore, not only the physicochemical characteristics, gene transfection efficiency, NPC-targeting capacity of the nanocomposite and its distribution in vivo tissue of NPC-bearing nude mice, but also the expression of mRNA and protein of TFPI-2 in FR positive HNE-1 cell before and after gene transfection、its toxicity in vivo and inhibiting effect on NPC in vitro and in vivo will be studied by HPLC, in vivo imaging, RT-PCR, Western-blot, MTT assay, flow cytometry, Matrigel invasion test, HE staining, immunohistochemistry and TUNEL. The purpose of this study is to explore the feasibility and validity of the molecular targeted dual-sensitive system co-delivering drug and gene to treat NPC, and provide an experimental basis for clinical application.