Ruan Gui-Xin, Chen Yu-Zhe, Yao Xing-Lei, Du Anariwa, Tang Gu-Ping, Shen You-Qing, Tabata Yasuhiko, Gao Jian-Qing
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.
Department of Clinical Laboratory, Inner Mongolia Peoples Hospital, 20 Zhaowuda Road, Huhehaote 010010, Inner Mongolia, People's Republic of China.
Acta Biomater. 2014 May;10(5):1847-55. doi: 10.1016/j.actbio.2014.01.012. Epub 2014 Jan 16.
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.
巨噬细胞是造血系统中可塑性最强的细胞，具有极大的功能多样性。它们已被广泛应用于抗炎、抗纤维化和抗癌治疗。然而，巨噬细胞的应用受到其工程化效率的限制。巨噬细胞甘露糖受体（MMR，CD206）是一种C型凝集素受体，在巨噬细胞上普遍表达，对甘露糖寡糖具有高亲和力。在本研究中，我们开发了一种对MMR具有特异性亲和力的新型非病毒载体。用精胺以约12%的接枝率对甘露聚糖进行阳离子化以递送DNA，并将其表征为一种稳定的递送系统。这种基于精胺-甘露聚糖（SM）的递送系统被评估为一种生物相容性载体，对小鼠巨噬细胞具有优异的转染效率，比精胺-支链淀粉高28.5倍，比聚乙烯亚胺高11.5倍，比Lipofectamine™ 2000高3.0倍。我们证实基于SM的巨噬细胞转染递送系统是MMR特异性的，并描述了该递送系统的细胞内转运。据我们所知，这是第一项使用SM证明甘露糖受体特异性基因递送系统的研究，从而突出了一种新型特异性非病毒递送载体在巨噬细胞工程中的潜力。
