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

作　　者：孙芬芬[1] 林辉[2] 涂克华[1,3] 王红军[1,3] 王利群[1,3] 

机构地区：[1]浙江大学高分子科学与工程学系,杭州310027 [2]浙江大学医学院附属邵逸夫医院,杭州310016 [3]浙江大学教育部高分子合成与功能构造重点实验室,杭州310027

出　　处：《高分子学报》2015年第5期535-541,共7页Acta Polymerica Sinica

基　　金：国家自然科学基金(基金号21074112)资助项目

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.Amphiphilic block eopolymers poly （ ethylene glycol）-co-poly （ glycidyl methacrylate） （ PEG-co- P（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 eopolymer PEG-P （GMA-API）. The weight-average molecular weight and polydispersity of PEG-P（GMA-API） were determined to be 17175 and 1.08 with 1H-NMR and GPC ,respectively. The resulted copolymers could self-assemble into spherical nano-mieelles directly in an aqueous medium. The critical micellization concentration （CMC） of the mieelles was 4×10^-2 g/L,which was significantly influenced by amino and imidazole groups. Dynamic light scattering （DLS） study showed the diameter of the mieelles was about 40 nm and the mieelle surface was always positively charged when the pH of the solution increased from 4 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 pH 7.4. The features of Hb-based micelles were spherical with a diameter of 40 nm,which was larger than that of blank mieelles （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 

分 类 号：TQ317[化学工程—高聚物工业] TB383.1[一般工业技术—材料科学与工程]