纳米载体靶向肿瘤相关巨噬细胞导入小干扰RNA抑制乳腺癌EMT的研究

Tumor-associated macrophages play an important role in tumor microenvironment. The prognosis is closely related to the enrichment of tumor-associated macrophages in breast cancer. Tumor-associated macrophages in tumor stroma promote epithelial-mesenchymal transition (EMT) and metastasis of tumor cells via secreting signaling molecules. This project aims to develop nanomaterials targeting tumor associated macrophages, combining with passive targeting feature of nanomaterials, to deliver small interfering RNA into tumor associated macrophages to inhibit EMT and metastasis of breast cancer. First, we develop and optimize nanomaterials for the delivery of small interfering RNA targeting tumor-associated macrophages. To observe the role of tumor-associated macrophages in cell adhesion, invasion, and EMT of the breast cancer in vitro, tumor-associated macrophages treated with small interfering RNA delivered by nanomaterials, and then co-cultures with breast cancer cells. Finally, to explore the effect of tumor-associated macrophages in metastasis of breast cancer in vivo, tumor-associated macrophages and breast cancer were co-implanted to nude mice, and then treated with small interfering RNA delivered by nanomaterials. This project offers the experimental basis for us to support the topic of tumor-associated macrophages regulation the metastasis of breast cancer and helps to develop new therapies with silencing CSF-1R or CCL18 by targeting tumor-associated macrophages in the treatment of breast cancer metastasis.

肿瘤相关巨噬细胞作为构造肿瘤微环境的重要组成部分与肿瘤的预后密切相关，乳腺癌中肿瘤相关巨噬细胞富集提示预后不良。肿瘤间质中的肿瘤相关巨噬细胞可通过分泌信号分子，促进肿瘤细胞EMT及转移。本项目旨在开发靶向肿瘤相关巨噬细胞的纳米材料载体，与纳米材料特有的被动靶向功能结合起来，探索纳米载体靶向肿瘤相关巨噬细胞导入小干扰RNA抑制乳腺癌EMT的研究。首先我们构建和优化能靶向肿瘤相关巨噬细胞的纳米材料作为小干扰RNA的输送载体。在体外利用纳米材料输送小干扰RNA到肿瘤相关巨噬细胞，并与乳腺癌细胞共同培养，观察对乳腺癌细胞粘附、侵袭和EMT的作用。最后，在肿瘤相关巨噬细胞和乳腺癌共种植模型中，研究纳米材料输送小干扰RNA到肿瘤相关巨噬细胞对乳腺癌EMT和转移的作用。该课题将为肿瘤相关巨噬细胞调控乳腺癌转移的理论提供实验依据，探索靶向肿瘤相关巨噬细胞沉默CSF1R或CCL18治疗乳腺癌转移的新疗法。

肿瘤相关巨噬细胞作为构造肿瘤微环境的重要组成部分与肿瘤的预后密切相关，乳腺癌中肿瘤相关巨噬细胞富集提示预后不良。肿瘤间质中的肿瘤相关巨噬细胞可通过分泌信号分子，促进肿瘤细胞EMT 及转移。本项目旨在开发靶向肿瘤相关巨噬细胞的纳米材料载体，与纳米材料特有的被动靶向功能结合起来，探索纳米载体靶向肿瘤相关巨噬细胞导入小干扰 RNA 抑制乳腺癌 EMT 的研究。项目组成功构建和优化能靶向肿瘤相关巨噬细胞的纳米材料作为小干扰 RNA 的输送载体。在体外利用纳米材料输送小干扰RNA 到肿瘤相关巨噬细胞，并与乳腺癌细胞共同培养，观察对乳腺癌细胞粘附、侵袭的作用。本课题将为肿瘤相关巨噬细胞调控乳腺癌转移的理论提供实验依据，探索靶向肿瘤相关巨噬细胞沉默 CCL18 治疗乳腺癌转移的新疗法。