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聚乙二醇嵌段树枝状聚赖氨酸共聚物的合成及其基因载体研究 被引量:6

Studies on the Synthesis of Poly(ethylene glycol)-b-dendritic Poly(l-lysine)s and Their Application as Gene Carriers
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摘要 采用液相多肽合成法制备得到窄分子量分布、结构可控的生物相容性聚乙二醇嵌段共聚树枝状聚赖氨酸阳离子功能大分子(PEG-b-Dendritic PLL).运用1HNMR核磁共振、凝胶电泳以及荧光淬灭滴定手段对所得阳离子两嵌段大分子的化学结构及其与质粒DNA(pDNA)结合作用与复合行为进行了研究.结果表明聚乙二醇嵌段树枝状聚赖氨酸与pDNA分子可以在缓冲溶液中形成稳定的胶束,pDNA与阳离子树枝赖氨酸嵌段通过静电相互作用形成胶束核,其水溶性聚乙二醇嵌段形成水溶性胶束壳,提高了阳离子大分子/pDNA复合胶束的稳定性.同时发现随着阳离子嵌段树枝状赖氨酸代数的增加,阳离子两嵌段大分子与pDNA的结合作用增强,有利于其作为基因转染生物功能载体的应用. New water-soluble diblock poly(ethylene glycol)-b-dendritic poly(l-lysine) with diverse dendritic generations were molecularly designed and synthesized with well-defined structures. The chemical structures of the diblock cationic copolymers were characterized by ^1H NMR. Furthermore, agarose gel electrophoresis and fluorescence titration assays were implemented to evaluate the plasmid DNA (pDNA) binding affinities of the synthesized new block copolymers, indicating higher DNA binding affinities of the diblock copolymers with 4 and 5 generation (PLL). Moreover, the dynamic light scattering was applied to characterize the polyplexes nanoparticles of the cationic carrier/pDNA, indicating the water-soluble PEG-b-dendritic PLL and pDNA could complex to form stable "core-shell" structure nanoparticles, and the biocompatible PEG shell could possibly decrease cytotoxicity of the complexed polyplexes nanoparticle during cell gene transfection. Therefore, these new structural diblock cationic macromolecules may be further developed as potential gene carriers with high efficacy.
出处 《化学学报》 SCIE CAS CSCD 北大核心 2007年第19期2181-2186,共6页 Acta Chimica Sinica
基金 国家自然科学基金(Nos.20204019 20574087) 国家重点基础973项目(No.2004CB518802)资助项目.
关键词 聚乙二醇嵌段树枝状赖氨酸 阳离子大分子 pDNA载体 凝胶电泳 荧光淬灭滴定 PEG-b-dendritic PLL cationic gene cartier agarose gel electrophoresis fluorescence titration polyplex nanoparticles
作者简介 E-mail:yhxu@situ.edu.cnE-mail:acao@mail.sioc.ac.cn;
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