Qi Yanxin, Li Taihang, Wang Yupeng, Wei Xing, Li Bin, Chen Xuesi, Xie Zhigang, Jing Xiabin, Huang Yubin
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.
University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.
Macromol Biosci. 2016 Jun;16(6):906-13. doi: 10.1002/mabi.201500460. Epub 2016 Mar 3.
Amphiphilic triblock copolymers mPEG-b-PMAC-b-PCL are synthesized using methoxyl poly(ethylene glycol), cyclic carbonic ester monomer including acryloyl group, and ε-caprolactone. Copolymers are self-assembled into core-shell micelles in aqueous solution. Thiolated hemoglobin (Hb) is conjugated with micelles sufficiently through thiol Michael addition reaction to form hemoglobin nanoparticles (HbNs) with 200 nm in diameter. The conjugation of Hb onto the micelle surface is further confirmed by X-ray photoelectron spectroscopy. Feeding ratio of copolymer micelles to Hb at 1:3 would lead to the highest hemoglobin loading efficiency 36.7 wt%. The UV results demonstrate that the gas transporting capacity of HbNs is well remained after Hb is conjugated with polymeric micelles. Furthermore, the obtained HbNs have no obvious detrimental effects on blood components in vitro. This system may thus have great potential as one of the candidates to be developed as oxygen carriers and provide a reference for the modification of protein drugs.
使用甲氧基聚（乙二醇）、含丙烯酰基的环状碳酸酯单体和ε-己内酯合成两亲性三嵌段共聚物甲氧基聚乙二醇-b-聚甲基丙烯酸缩水甘油酯-b-聚己内酯。共聚物在水溶液中自组装成核壳胶束。通过硫醇-迈克尔加成反应，使硫醇化血红蛋白（Hb）与胶束充分共轭，形成直径为200nm的血红蛋白纳米颗粒（HbNs）。通过X射线光电子能谱进一步证实了Hb在胶束表面的共轭。共聚物胶束与Hb的投料比为1:3时，血红蛋白负载效率最高，为36.7 wt%。紫外结果表明，Hb与聚合物胶束共轭后，HbNs的气体运输能力得到了很好的保留。此外，所获得的HbNs在体外对血液成分没有明显的有害影响。因此，该系统作为氧载体开发的候选之一可能具有巨大潜力，并为蛋白质药物的修饰提供参考。
