Targeting folate receptor β positive tumor-associated macrophages in lung cancer with a folate-modified liposomal complex
| العنوان: | Targeting folate receptor β positive tumor-associated macrophages in lung cancer with a folate-modified liposomal complex |
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| المؤلفون: | Zhiyao He, Xiangxian Zhang, Li Liu, Yan Tie, Xiawei Wei, Min Wu, Yu Liu, Hongyi Li, Min Luo, Bin Shao, Jingyun Yang, Xia Yuan, Heng Zheng |
| المصدر: | Signal Transduction and Targeted Therapy Signal Transduction and Targeted Therapy, Vol 5, Iss 1, Pp 1-15 (2020) |
| بيانات النشر: | Nature Publishing Group UK, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Lung Neoplasms, Angiogenesis, medicine.medical_treatment, lcsh:Medicine, Apoptosis, Article, Metastasis, Targeted therapy, Mice, 03 medical and health sciences, Prognostic markers, Folic Acid, 0302 clinical medicine, Tumor-Associated Macrophages, Tumor Microenvironment, Genetics, medicine, Animals, Humans, Folate Receptor 2, Lung cancer, lcsh:QH301-705.5, Cell Proliferation, Tumor microenvironment, business.industry, lcsh:R, Cancer, medicine.disease, 030104 developmental biology, lcsh:Biology (General), A549 Cells, Folate receptor, 030220 oncology & carcinogenesis, Liposomes, Cancer research, lipids (amino acids, peptides, and proteins), business |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 2059-3635 2095-9907 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4721efc600e486cab95836dcb03c2af1Test http://europepmc.org/articles/PMC6976681Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4721efc600e486cab95836dcb03c2af1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20593635 20959907 |
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