研究证实热休克蛋白HSP70B启动子是加热诱导基因表达的“分子开关”，我们据此构建出一系列热调控的表达质粒。然而，加热诱导基因治疗的瓶颈在于缺乏理想的表达质粒传递载体。本项目以超支化聚合物作为基础，提出融合热诱导基因和热敏材料的思路，尝试两者协同进行肿瘤基因治疗的研究。选择聚酰胺-胺类树枝状大分子和超支化聚乙烯亚胺，引发多巴胺聚合为聚多巴胺，并于表面修饰靶向配体RGD修饰，使其具有肿瘤靶向性；然后引入含HSP70B启动子及报告基因以及TNF-α肿瘤杀伤基因的表达质粒，创建新型携带热诱导调控的肿瘤细胞靶向性过渡金属硫化物基因治疗平台，在体内外进行功效验证。新型平台不但是基因传递的载体，也可以作为细胞内热疗的发热介质，并且能够实现治疗基因的可视化成像，观察治疗基因是否有效传递到肿瘤靶区域以及组织内基因的相对浓度变化，以有效监控肿瘤基因治疗，搭建基因材料和临床应用之间的桥梁。

Heating can selectively induce targeted gene expression in desired organs or tissues. It has been proven that heat shock protein 70 promoter is the "molecular switch" of gene expression, and we have set up a series of heat inducible expression plasmids. However the bottle neck of heat-inducible gene therapy is the deficiency of ideal expression plasmid vector. On the basis of the excellent genen delivery and transfection of hyperbranched polymer, a new idea is developed in this program to merge heat-inducible gene and thermosensitive materials in the treatment of tumors. RGD peptide is introduced to the surface of hyperbranched polymer, and then connected to heat shock protein 70 promoter plasmids containing reporter genes and tumor necrosis factor-α gene. After building this new integrated heat-inducible gene and RGD targeted hyperbranched polymer platform for cancer, its efficiency will be tested and evaluated both in vivo and ex vivo. This novel platform is not only an ideal expression plasmid vector, but also an intracellular medium of thermotherapy. In addition, as a virtualization tool this platform can be applied to trace and monitor whether or not the therapeutic gene into the tumor area and relative concentration of the expression gene. Therefore, this program is bridging the gap between biological research and clinical application.