吉西他滨(GEM)是进展期和转移性胰腺癌的一线化疗药，因耐药使疗效丧失，其分子机制主要是由于人类平衡型核苷转运蛋白1(hENT1)表达下降导致GEM胞内转运减少，降低了GEM对细胞周期的阻滞作用。本研究拟构建重组双基因质粒载体pLV-Dual-MUC1-hENT1/hNIS (MUC1为胰腺癌特异性启动子)，并装至基于酸性微环境解离的复合纳米颗粒PLLA-MSN-CaCO3，在细胞水平和组织水平双重靶向递送目的基因，特异性上调hENT1表达，促进GEM胞内转运，抑制细胞增殖，使耐药胰腺癌细胞恢复化疗敏感性；同时利用hNIS介导123I报告基因显像定位治疗基因。利用FLT与GEM的部分代谢相似性，通过18F-FLT Micro PET/CT动静态显像，在分子水平监测hENT1功能和细胞增殖活性，实现基因增敏治疗可视化精准评估。

Gemcitabine (GEM) is the first-line chemotherapy medicament for advanced and metastatic pancreatic cancer. But the appearance of chemotherapy resistance results in a greatly reduced therapy effect. The major molecular mechanism is due to the decrease of human equilibrative nucleoside transporter 1(hENT1), which results in the reduction of intracellular retention of GEM and the blocking effect of GEM on cell cycle is not sufficient. This study intends to construct a recombinant plasmid vector, pLV-Dual-MUC1-hENT1/hNIS (MUC1 is an evident targeting effect in pancreatic tumors). At the same time, the lentivirus will be loaded into the complex nanoparticles PLLA-MSN-CaCO3, which were dissociated in acidic microenvironment. This composite carrier is permitted the target genes delivered to drug-resistant pancreatic cancer cells at the cellular and tissue levels, which can specifically upregulate the expression of hENT1, promote the intracellular transport of GEM and inhibite cell proliferation. Meanwhile, hNIS is aimed to induce 123I reporter gene imaging, which is used to locate the therapeutic gene. According to the similar metabolic pathway of FLT and GEM, 18F-FLT is used for Micro PET/CT dynamic and static imaging. We can monitor the function of hENT1 and observe cell proliferation activity with that noninvasive method in vivo on molecular level, which realizes visual evaluation of chemo-sensitization.