机构：[1]Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041 Sichuan, PR China四川大学华西医院[2]Department of Oncology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041 Sichuan, PR China四川省人民医院四川省肿瘤医院[3]Department of Gynecology and Obstetrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second Hospital, Sichuan University, Chengdu 610041 Sichuan, PR China[4]Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58202, USA
Tumor-associated macrophages (TAMs) facilitate cancer progression by promoting tumor invasion, angiogenesis, metastasis, inflammatory responses, and immunosuppression. Folate receptor beta (FR beta) is overexpressed in TAMs. However, the clinical significance of FR beta-positive macrophages in lung cancer remains poorly understood. In this study, we verified that FR beta 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 FR beta-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 FR beta-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.
基金：
National Key Research and Development Program of China [2016YFA0201402]; National Major Scientific and Technological Special Project for "Significant New Drugs Development" of China [2018ZX09733001]; Excellent Youth Foundation of Sichuan Scientific Committee Grant in China [2019JDJQ008]
第一作者机构：[1]Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041 Sichuan, PR China[2]Department of Oncology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041 Sichuan, PR China
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推荐引用方式(GB/T 7714)：
Tie Yan,Zheng Heng,He Zhiyao,et al.Targeting folate receptor beta positive tumor-associated macrophages in lung cancer with a folate-modified liposomal complex[J].SIGNAL TRANSDUCTION AND TARGETED THERAPY.2020,5(1):doi:10.1038/s41392-020-0115-0.
APA：
Tie Yan,Zheng Heng,He Zhiyao,Yang Jingyun,Shao Bin...&Wei Xiawei.(2020).Targeting folate receptor beta positive tumor-associated macrophages in lung cancer with a folate-modified liposomal complex.SIGNAL TRANSDUCTION AND TARGETED THERAPY,5,(1)
MLA：
Tie Yan,et al."Targeting folate receptor beta positive tumor-associated macrophages in lung cancer with a folate-modified liposomal complex".SIGNAL TRANSDUCTION AND TARGETED THERAPY 5..1(2020)
医学