Rational Design of Anti-inflammatory Polymers Inspired by Apoptotic Cell Death using Phosphoramidite Chemistry
Rational Design of Anti-inflammatory Polymers Inspired by Apoptotic Cell Death using Phosphoramidite Chemistry
复制标题
利用亚磷酰胺化学合理设计受凋亡细胞死亡启发的抗炎聚合物
DOI：
10.1016/j.polymer.2017.11.031
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发表时间：
2018
期刊：
影响因子：
4.6
通讯作者：
Mitsuhiro Ebara
中科院分区：
文献类型：
--
作者：
Yasuhiro Nakagawa;Atsuhiro Saitou;Takao Aoyagi;Mitsuhiro Ebara
我们在这里提出了一个合理的方法来设计具有免疫抑制作用的抗炎治疗聚合物。已经揭示，凋亡细胞修饰免疫细胞的形态以通过其表面上的外部化磷脂酰丝氨酸表达免疫抑制表型。受此现象的启发，凋亡细胞膜启发的聚合物被修饰后聚合与磷酰丝氨酸（PS）基团。在这项研究中，我们应用亚磷酰胺的方法，四种常用的聚合物在生物材料：共聚物的N-异丙基丙烯酰胺，甲基丙烯酸丁酯，以及聚（ε-己内酯），和泊洛沙姆。通过1H NMR、31 P NMR和凝胶渗透色谱（GPC）证实了PS基团的成功加入，并通过小鼠巨噬细胞证明了它们的细胞毒性和免疫抑制作用。PS修饰的聚合物被发现成功地保护巨噬细胞免受脂多糖诱导的炎症。我们相信，所提出的设计有望为开发先进的免疫抑制剂和抗炎治疗材料打开新的大门，因为PS修饰对各种材料具有高度通用性。
We propose here a rational approach to design polymers with immunosuppressive effects for anti-inflammatory therapies. It has been revealed that apoptotic cells modify the morphology of immune cells to express immunosuppressive phenotypes via externalized phosphatidylserine on their surface. Inspired by this phenomenon, apoptotic cell membrane-inspired polymers were modified post-polymerization with phosphoryl serine (PS) groups. In this study, we applied the phosphoramidite method to four commonly used polymers in biomaterials: copolymers ofN-isopropylacrylamide, butyl methacrylate, as well as poly(ε-caprolactone), and poloxamers. The successful addition of PS groups was confirmed by1H NMR spectroscopy,31P NMR spectroscopy and, gel-permeation chromatography (GPC), and their cytotoxicity and immunosuppressive effects were demonstrated using murine macrophage cells. PS-modified polymers were found to successfully protect macrophages from lipopolysaccharide-induced inflammation. We believe that the proposed design is expected to open new doors in developing advanced immunosuppressive agents and materials for anti-inflammatory therapies as PS-modification is highly versatile for a variety of materials.