Macrophage mannose receptor-specific gene delivery vehicle for macrophage engineering.
Macrophages are the most plastic cells in the hematopoietic system and they exhibit great functional diversity. They have been extensively applied in anti-inflammatory, anti-fibrotic and anti-cancer therapies. However, the application of macrophages is limited by the efficiency of their engineering. The macrophage mannose receptor (MMR, CD206), a C-type lectin receptor, is ubiquitously expressed on macrophages and has a high affinity for mannose oligosaccharides. In the present study, we developed a novel non-viral vehicle with specific affinity for MMR. Mannan was cationized with spermine at a grafted ratio of ∼12% to deliver DNA and was characterized as a stable system for delivery. This spermine-mannan (SM)-based delivery system was evaluated as a biocompatible vehicle with superior transfection efficiency on murine macrophages, up to 28.5-fold higher than spermine-pullulan, 11.5-fold higher than polyethylenimine and 3.0-fold higher than Lipofectamine™ 2000. We confirmed that the SM-based delivery system for macrophages transfection was MMR-specific and we described the intracellular transport of the delivery system. To our knowledge, this is the first study using SM to demonstrate a mannose receptor-specific gene delivery system, thereby highlighting the potential of a novel specific non-viral delivery vehicle for macrophage engineering.
Zhejiang Province Key Laboratory of Anti-Cancer Research, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, Zhejiang, People's Republic of China.
Gui-Xin
GX
Ruan
Zhejiang Province Key Laboratory of Anti-Cancer Research, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, Zhejiang, People's Republic of China.
Yu-Zhe
YZ
Chen
Zhejiang Province Key Laboratory of Anti-Cancer Research, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, Zhejiang, People's Republic of China.
Xing-Lei
XL
Yao
Department of Clinical Laboratory, Inner Mongolia Peoples Hospital, 20 Zhaowuda Road, Huhehaote 010010, Inner Mongolia, People's Republic of China.
Anariwa
A
Du
Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou, People's Republic of China.
Gu-Ping
GP
Tang
Center for Bionanoengineering and State Key Laboratory of Chemical Engineering, Zhejiang University, Hangzhou 310027, People's Republic of China.
You-Qing
YQ
Shen
Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
Yasuhiko
Y
Tabata
Zhejiang Province Key Laboratory of Anti-Cancer Research, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, Zhejiang, People's Republic of China. Electronic address: gaojianqing@zju.edu.cn.
Jian-Qing
JQ
Gao
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D060846:Cell Engineering / Q000379:methods*; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008351:Mannans / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013055:Spectrophotometry, Infrared; D013096:Spermine / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D014162:Transfection
D037181:Lectins, C-Type; D008351:Mannans; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D013096:Spermine; D004247:DNA; D008156:Luciferases
Gene delivery; Macrophage; Mannose receptor; Spermine–mannan