靶向化疗及基因治疗已经成为肿瘤治疗研究热点，但目前尚未见联合放疗、化疗、靶向基因综合治疗鼻咽癌（NPC）的研究。本项目在前两项国家自然科学基金资助基础上，拟采用化学方法制备偶联顺铂（CDDP）的叶酸靶向PEG-PEI-Alg-磁性纳米粒（FA-MNP-CDDP），吸附表达绿色荧光蛋白和TFPI-2质粒的复合物联合放疗对NPC进行综合靶向治疗。通过HPLC、原子吸收光谱法、RT-PCR及Western-blot法、流式细胞术、Matrigel侵袭实验、细胞克隆实验、免疫组化、TUNEL法等，研究该磁性纳米复合物的理化特征、基因转染效率、对NPC的靶向性、在荷鼻咽癌裸鼠体内的分布、转染前后叶酸受体阳性HNE-1细胞TFPI-2 mRNA和蛋白表达、以及联合放疗对NPC的体内外抑制效应。探索分子靶向综合治疗方法的可行性和有效性，为临床应用提供实验依据。

Targeted chemotherapy and gene therapy have become two research hotspots for the treatment of tumor, but so far, no report is found on combined radiotherapy, targeted chemotherapy and gene therapy for nasopharyngeal carcinoma (NPC). On the basis of the first two items of National Natural Science Funds, folic acid targeting PEG-PEI-Alg-Fe3O4 magnetic nanoparticle coupling cisplatin (FA-MNP-CDDP) will be prepared by chemical method, and the composite of FA-MNP-CDDP adsorbing TFPI-2-green fluoresent protein expression vector will be used for targeted therapy combined with radiotherapy for NPC in this project. Furthermore, not only the physicochemical characteristics, gene transfection efficiency, capacity of targeting NPC of the magnetic nanocomposite and its distribution in tissue of NPC-bearing nude mice, but also the expression of mRNA and protein of TFPI-2 in folic receptor (FR) positive HNE-1 cell before and after gene transfection as well as the inhibiting effect of the composites combined with radiotherapy for NPC in vitro and in vivo will be studied by HPLC, atomic absorption spectrometry, RT-PCR, Western-blot, flow cytometry, Matrigel invasion test, cell cloning, immunohistochemistry and TUNEL. The purpose of this study is to explore the feasibility and validity of combined molecular targeted therapy for NPC, and provide an experimental basis for clinical application.