Targeting folate receptor β positive tumor-associated macrophages in lung cancer with a folate-modified liposomal complex.,Signal Transduction and Targeted Therapy

当前位置： X-MOL 学术 › Signal Transduct. Target Ther. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Targeting folate receptor β positive tumor-associated macrophages in lung cancer with a folate-modified liposomal complex.
Signal Transduction and Targeted Therapy ( IF 40.8 ) Pub Date : 2020-01-22 , DOI: 10.1038/s41392-020-0115-0
Yan Tie _{1,

2} , Heng Zheng ₃ , Zhiyao He ₁ , Jingyun Yang _{1,

3} , Bin Shao ₁ , Li Liu ₁ , Min Luo ₁ , Xia Yuan ₁ , Yu Liu ₁ , Xiangxian Zhang ₁ , Hongyi Li ₃ , Min Wu ₄ , Xiawei Wei ₁

Affiliation

Tumor-associated macrophages (TAMs) facilitate cancer progression by promoting tumor invasion, angiogenesis, metastasis, inflammatory responses, and immunosuppression. Folate receptor β (FRβ) is overexpressed in TAMs. However, the clinical significance of FRβ-positive macrophages in lung cancer remains poorly understood. In this study, we verified that FRβ overexpression in lung cancer TAMs was associated with poor prognosis. We utilized a folate-modified lipoplex comprising a folate-modified liposome (F-PLP) delivering a BIM-S plasmid to target both lung cancer cells and FRβ-positive macrophages in the tumor microenvironment. Transfection of LL/2 cells and MH-S cells with F-PLP/pBIM induced cell apoptosis. Injection of F-PLP/pBIM into LL/2 and A549 lung cancer models significantly depleted FRβ-positive macrophages and reduced tumor growth. Treatment of tumor-bearing mice with F-PLP/pBIM significantly inhibited tumor growth in vivo by inducing tumor cell and macrophage apoptosis, reducing tumor proliferation, and inhibiting tumor angiogenesis. In addition, a preliminary safety evaluation demonstrated a good safety profile of F-PLP/pBIM as a gene therapy administered intravenously. This work describes a novel application of lipoplexes in lung cancer targeted therapy that influences the tumor microenvironment by targeting TAMs.

中文翻译：

用叶酸修饰的脂质体复合物靶向肺癌中叶酸受体 β 阳性肿瘤相关巨噬细胞。

肿瘤相关巨噬细胞（TAM）通过促进肿瘤侵袭、血管生成、转移、炎症反应和免疫抑制来促进癌症进展。叶酸受体 β (FRβ) 在 TAM 中过度表达。然而，FRβ阳性巨噬细胞在肺癌中的临床意义仍知之甚少。在这项研究中，我们证实肺癌 TAM 中 FRβ 过度表达与不良预后相关。我们利用包含叶酸修饰脂质体 (F-PLP) 的叶酸修饰脂质复合物，传递 BIM-S 质粒来靶向肿瘤微环境中的肺癌细胞和 FRβ 阳性巨噬细胞。用 F-PLP/pBIM 转染 LL/2 细胞和 MH-S 细胞诱导细胞凋亡。将 F-PLP/pBIM 注射到 LL/2 和 A549 肺癌模型中可显着耗尽 FRβ 阳性巨噬细胞并减少肿瘤生长。用F-PLP/pBIM治疗荷瘤小鼠，通过诱导肿瘤细胞和巨噬细胞凋亡、减少肿瘤增殖、抑制肿瘤血管生成，显着抑制体内肿瘤生长。此外，初步安全性评估表明，F-PLP/pBIM 作为静脉注射基因疗法具有良好的安全性。这项工作描述了 lipoplex 在肺癌靶向治疗中的一种新应用，通过靶向 TAM 来影响肿瘤微环境。

更新日期：2020-01-22

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文