含醛基可降解嵌段共聚物的合成及其生物缀合  

Synthesis of Aldehyde Functionalized and Degradable Block Copolymers and Their Bioconjugation

作　　者：黄建兵[1] 肖中鹏[1] 梁晖[1] 卢江[1] 

机构地区：[1]中山大学化学与化学工程学院,广州510275

出　　处：《高分子学报》2015年第4期459-465,共7页Acta Polymerica Sinica

基　　金：国家然科学基金(基金号21074150;2127416)资助项目

摘　　要：以PEO-DDMAT为大分子RAFT试剂、BPO为引发剂,调控含醛基单体4-乙烯基苯甲醛(VBA)与不饱和环缩醛单体5,6-苯基-2-亚甲基-1,3-二氧七环(BMDO)的RAFT共聚合,获得一种新型含醛基、可降解的两亲性嵌段共聚物PEO-b-poly(VBA-co-BMDO),并对不同单体投料比下的共聚行为进行了研究.由于聚合物主链含有酯基,可以在水中碱性条件下进行降解.细胞毒性分析表明其具有良好生物相容性.该嵌段聚合物还可以通过醛基-氨氧基"点击"反应和模型生物分子氨氧基胆固醇(H2NO-Chol)形成稳定的聚合物-生物分子缀合物,该缀合物能在水溶液中自组装成纳米胶束.结果表明PEO-b-poly(VBA-co-BMDO)可以作为聚合物载体缀合含氨氧基的药物分子,在生物医药方面有良好的应用前景.A well-defined degradable and aldehyde-functionalized amphiphilic block copolymer PEO-b- poly（VBA-co-BMDO） with narrow molecular weight distribution （Mw/Mn 〈 1.20） was synthesized via reversible addition-fragmentation chain transfer （RAFT） copolymerization of 4-vinylbenzaldehyde （VBA） and 5,6-benzo-2-methylene-1,3-dioxepane （BMDO） using PEO-DDMAT as chain transfer agent and benzoyl peroxide （BPO） as initiator at 80 ℃ in 2-butanone. Copolymers with variable amounts of BMDO or VBA units could be obtained just by changing the feed composition. The obtained amphiphilic block copolymers were found to be hydrolytically degradable due to the main-chain polyester structure. Low eytotoxicity against L929 cells was observed at polymer concentration up to 1.0 mg mL^-1, indicating that amphiphilic block copolymer PEO-b-poly（VBA-co-BMDO） exhibits good biocompatibility. The highly reactive aldehyde functions in the synthesized amphiphilic block eopolymer could provide the key intermediates to conjugate biomolecules, and the availability of the amphiphilic block copolymer to conjugate bioactive molecules was confirmed via aldehyde-aminooy click reaction with an aminooxy model drug, aminooxy functionalized cholesterol （H2NO- Chol）. The successful conjugate formation was demonstrated by GPC and ^1H-NMR analyses. Self-assemblies in water of the amphiphilic block copolymer PEO-b-poly（VBA-co-BMDO） and its bioconjugate were also investigated by dynamic light scattering （DLS） and scanning electron microscopy （SEM） measurements. The conjugates of PEO-b-poly（VBA-co-BMDO） with cholesterol could self-assemble into spherical micelles in aqueous solution with size in the range of 70 - 110 nm. These results suggested that the amphiphilic copolymer PEO-b-poly（VBA-co-BMDO） would be useful as a versatile polymer scaffold for bioconjugating.

关 键 词：醛基 可降解 RAFT共聚 生物缀合 

分 类 号：O631.1[理学—高分子化学]