我们前期研究发现胰腺癌间质富含促癌M2型肿瘤相关巨噬细胞（TAMs，CD163+），其在体外被胰腺癌细胞（可能经IL-6）诱导分泌SDF-1，SDF-1又促进胰腺癌细胞侵袭，该作用可被SDF-1受体CXCR4阻断剂AMD3100阻断，因此，M2型TAMs与癌细胞间可能存在SDF-1/CXCR4/IL-6正反馈环路。此外，上调富含组氨酸糖蛋白（HRG）基因可诱导M2型TAMs向抑癌M1型转化。本研究将深入探讨和验证上述环路作用机制；并用我们已建立纳米技术针对此新靶点及M2型TAMs构建胰腺癌靶向治疗纳米载体：①含人源CD163单链抗体；②载HRG基因，同时用可裂解肽将AMD3100与载体相连；③此新型纳米载体可将HRG基因靶向导入M2型TAMs，诱使其向M1型转化；并局部释放AMD3100，阻断M2型TAMs与癌细胞互惠作用，在人源化鼠原位癌模型双靶点调控肿瘤微环境，为治疗胰腺癌提供新思路。

Previous studies have found that there are a large number of M2 type of tumor associated macrophage cells (TAMs, CD163 +) in the pancreatic cancer (PC) stroma, which may induce SDF-1 cytokine secretion through IL-6 in vitro. What is more, SDF-1 cytokine can further promote the invasion of PC cells. Consequently, we hypothesis that there may be a SDF-1/ CXCR4 / IL-6 positive feedback loop between M2-TAMs and PC cells. In addition, it is reported that overexpressing HRG can induce transformation of M2 type of TAMs to M1 type. In this study, we will further study the function and molecular mechanisms of this loop; using the nanotechnology we have already established build a nanoparticle delivery system for PC targeted therapy: ① including human single-chain antibody CD163; ② nanoparticles loading drug and histidine glycoprotein (HRG) gene. Cracking peptide can connect AMD3100 with the nanoparticles; ③ the increasing of HRG gene can induce M2-TAMs transformation to M1 type cells which act as tumor-suppressor. This new nanoparticles can target HRG gene to M2-TAMs, and induce M2-TMA2 cells to transform to M1 type; At the same time, this nanoparticle system can also release AMD3100, as a result blocking the reciprocal loop between PC and M2-TAM2, and finally double targeted control the micro-environment of PC tumor in humanized mouse model, providing a new way for the treatment of PC.