title: Targeted delivery of let-7b to reprogramme tumor-associated macrophages and tumor infiltrating dendritic cells for tumor rejection.
abstract: Both tumor associated macrophages (TAMs) and tumor infiltrating dendritic cells (TIDCs) are important components in the tumor microenvironment that mediate tumor immunosuppression and promote cancer progression. Targeting these cells and altering their phenotypes may become a new strategy to recover their anti-tumor activities and thereby restore the local immune surveillance against tumor. In this study, we constructed a nucleic acid delivery system for the delivery of let-7b, a synthetic microRNA mimic. Our carrier has an affinity for the mannose receptors on TAMs/TIDCs and is responsive to the low-pH tumor microenvironment. The delivery of let-7b could reactivate TAMs/TIDCs by acting as a TLR-7 agonist and suppressing IL-10 production in vitro. In a breast cancer mouse model, let-7b delivered by this system efficiently reprogrammed the functions of TAMs/TIDCs, reversed the suppressive tumor microenvironment, and inhibited tumor growth. Taken together, this strategy, designed based upon TAMs/TIDCs-targeting delivery and the dual biological functions of let-7b (TLR-7 ligand and IL-10 inhibitor), may provide a new approach for cancer immunotherapy.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Gan
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China.
authors.forename: Ziyan
authors.initials: Z
authors.lastname: Long
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China.
authors.forename: Guangxing
authors.initials: G
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China.
authors.forename: Xiafei
authors.initials: X
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China.
authors.forename: Chunming
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Zang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China.
authors.forename: Jiangning
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China. Electronic address: jfzhang@nju.edu.cn.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China. Electronic address: leidong@nju.edu.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
mesh_terms: D000818:Animals; D001940:Breast / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D002478:Cells, Cultured; D000067470:Cellular Reprogramming Techniques / Q000379:methods; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007167:Immunotherapy; D016753:Interleukin-10 / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D051199:Toll-Like Receptor 7 / Q000276:immunology; D059016:Tumor Microenvironment
chemical_list: D035683:MicroRNAs; D051199:Toll-Like Receptor 7; C542687:mirnlet7 microRNA, mouse; D016753:Interleukin-10
keywords: Cancer immunotherapy; Let-7b; Targeted delivery; Tumor-associated macrophage; Tumor-infiltrating dendritic cell