Zhao Xiaotian, Li Xiaoming, Zhao Yi, Cheng Yuan, Yang Yunqi, Fang Zhiwei, Xie Yangmei, Liu Yao, Chen Yinghui, Ouyang Yuanming, Yuan Weien
School of Pharmacy, Shanghai Jiao Tong UniversityShanghai, China.
Department of Neurology, Jinshan Hospital, Fudan UniversityShanghai, China.
Front Pharmacol. 2017 Aug 4;8:510. doi: 10.3389/fphar.2017.00510. eCollection 2017.
Polycationic vectors are used widely in the field of gene delivery, while currently their immune activities are poorly understood. In this comprehensive review, we aim to present an overview of existing mechanisms of adverse immune responses induced by the polycation/gene complexes, which includes the polycations themselves, the gene sequences and the ROS produced by them. These causes can induce pro-inflammatory cytokines, hypersensitivity as well as the activation of toll-like receptors, and finally the immunostimulation occur. In addition, we introduce some different opinions and research results on the immunogenicity of classical polycations such as polylysine (PLL), polyethyleneimine (PEI), polyamidoamine dendrimers (PAMAM), chitosan and gelatin, most of which have immunogenicity and can induce immunoreactions . The methods now used to adjust their immunogenicity are shown in the final part of this review. Nowadays, there is still no accurate conclusion on immunogenicity of polycations, which confuses researchers seriously in test. We conclude that further research is needed in order to skillfully utilize or inhibit the immunogenicity of these polycationic vectors.
聚阳离子载体在基因递送领域被广泛应用,然而目前对其免疫活性的了解却很少。在这篇综述中,我们旨在概述由聚阳离子/基因复合物诱导的不良免疫反应的现有机制,其中包括聚阳离子本身、基因序列以及它们产生的活性氧。这些因素可诱导促炎细胞因子、超敏反应以及Toll样受体的激活,最终引发免疫刺激。此外,我们介绍了一些关于经典聚阳离子如聚赖氨酸(PLL)、聚乙烯亚胺(PEI)、聚酰胺胺树枝状大分子(PAMAM)、壳聚糖和明胶免疫原性的不同观点和研究结果,其中大多数具有免疫原性并可诱导免疫反应。本综述的最后部分展示了目前用于调节其免疫原性的方法。如今,关于聚阳离子的免疫原性仍没有准确的结论,这在试验中严重困扰着研究人员。我们得出结论,需要进一步研究以便巧妙地利用或抑制这些聚阳离子载体的免疫原性。