清除或抑制肿瘤干细胞是防止肿瘤复发/或转移的关键。我们的前期研究表明；重组甲硫氨酸酶（rMETase）可以有效干扰胃癌细胞的甲硫氨酸代谢，抑制胃癌细胞的增殖，诱发其凋亡。但rMETase对胃癌干细胞生物效应如何尚不清楚。最新研究发现，去甲基化调控可以抑制氟尿嘧啶类耐药基因TFAP2E表达，增加5-Fu 的抗肿瘤效果。我们推测：具有去甲基化作用的rMETase与5-Fu联合具有协同抗肿瘤效应。基于此新设想，本项目在前期成功构建纳米载体的基础上，构建具有主动靶向胃癌干细胞的人源anti-CD44单链抗体介导的rMETase/5-Fu双药隐形纳米粒子, 采用体外培养以及体内实验方法，评估其对胃癌干细胞自我更新、致瘤能力、细胞周期调控及凋亡的影响并探索分子机制。所得的结果将为胃癌的靶向治疗提供新的思路和切入点，具有重要的理论意义和潜在的临床应用前景。

To clear cancer stem cells is the key of preventing tumor recurrence and/or transfer.Our previous studies show that recombinant methioninase can effectively interference methionine metabolism of gastric cancer cells and inhibit gastric cancer cell proliferation and induce its apoptosis. But biological effect of rMETase to gastric cancer stem cell is not clear. A new study has found that demethylation regulation can restrain TFAP2E expression, increasing anti-tumor effect of 5-Fu. We hypothesized that rMETase has collaborative antitumor effect with 5-Fu because of its effect of demethylation. Based on this new idea, the project construct human anti- CD44-scFv- rMETase / 5-Fu complex nanoparticles targeting gastric cancer stem cell in the basis of successfully constructing nanoparticles.Then we evaluate the influence of anti- CD44-scfv- rMETase / 5-Fu complex nanoparticles to the gastric cancer stem cell in ability of self-renewal or tumorigenicity or cell cycle regulation or apoptosis in vitro and in vivo and explore the molecular mechanism. The results has important theoretical significance and potential clinical application prospect. At the same time, it will be provide new ideas for targeted therapy of gastric cancer.