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载血红蛋白纳米胶束的制备及蛋白封装行为研究

Preparation of Hemoglobin-loaded Polymer Micelles as Artificial Oxygen Carrier

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【作者】 孙芬芬林辉涂克华王红军王利群

【Author】 Fen-fen Sun;Hui Lin;Ke-hua Tu;Hong-jun Wang;Li-qun Wang;Department of Polymer Science and Engineering,Zhejiang University;Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University;MOE Key Laboratory of Macromolecular Synthesis and Functionalization,Zhejiang University;

【机构】 浙江大学高分子科学与工程学系浙江大学医学院附属邵逸夫医院浙江大学教育部高分子合成与功能构造重点实验室

【摘要】 通过原子转移自由基聚合(ATRP)制备了两亲性嵌段共聚物聚乙二醇-聚甲基丙烯酸缩水甘油酯PEG-b-P(GMA)45,利用1-(3-氨基丙基)咪唑(API)与GMA上的环氧基发生开环反应,合成了聚乙二醇-聚(咪唑丙基-1-胺-甲基丙烯酸羟丙酯)PEG-P(GMA-API)45.研究表明,该聚合物可以直接在水中自组装形成均匀的球形纳米胶束,粒径约为40 nm.由于咪唑基的p H响应性,胶束表面在p H从4增大到9的范围内均带正电荷,p H 7.4时共聚物可以与血红蛋白产生较强的静电作用和氢键作用,达到包载血红蛋白的目的.同时还研究了聚合物对不同比例血红蛋白的包封率,当聚合物与血红蛋白的质量比为1∶1时包封率最高,为32.4wt%.UV-Vis显示包封后的血红蛋白在不同气体结合状态的特征吸收峰与自由血红蛋白差别不大,表明载血红蛋白纳米胶束具有良好的气体运输能力,PEG-P(GMA-API)45纳米胶束将有可能用于新型的人工氧载体.

【Abstract】 Amphiphilic block copolymers poly( ethylene glycol)-co-poly( glycidyl methacrylate)( PEG-coP( GMA)) were synthesized via atom transfer radical polymerization( ATRP). Postpolymerization decoration of reactive epoxy groups in the P( GMA) block with N-( 3-amino propyl) imidazole( API) resulted in a new kind of water soluble copolymer PEG-P( GMA-API). The weight-average molecular weight and polydispersity of PEG-P( GMA-API) were determined to be 17175 and 1. 08 with1H-NMR and GPC,respectively. The resulted copolymers could self-assemble into spherical nano-micelles directly in an aqueous medium. The critical micellization concentration( CMC) of the micelles was 4 × 10- 2g / L,which was significantly influenced by amino and imidazole groups. Dynamic light scattering( DLS) study showed the diameter of the micelles was about 40 nm and the micelle surface was always positively charged when the p H of the solution increased from4 to 9. The resulted nano-micelles had the capacity to encapsulate hemoglobin( Hb) in aqueous solution with the encapsulation efficiency of 32. 4 wt% at p H 7. 4. The features of Hb-based micelles were spherical with a diameter of 40 nm,which was larger than that of blank micelles( 30 nm). The Hb-based micelles displayed a reversible change in the UV-Visible absorption spectrum from the deoxy form to the oxygen-binding one,in response to the partial oxygen pressure of the atmosphere. The characteristic absorption peaks of the encapsulated Hb in different gas-binding states showed no significant change comparing with those of the free Hb. The Hb encapsulated PEG-P( GMA-API) nano-micelles showed the potential application as artificial oxygen carriers for transfusion.

【关键词】 ATRP纳米胶束咪唑血红蛋白人工氧载体
【Key words】 ATRPNano-micelleImidazoleHbArtificial oxygen carrier
【基金】 国家自然科学基金(基金号21074112)资助项目
  • 【文献出处】 高分子学报 ,Acta Polymerica Sinica , 编辑部邮箱 ,2015年05期
  • 【分类号】TQ317;TB383.1
  • 【被引频次】1
  • 【下载频次】224
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