Phosphorylcholine-polycation diblock copolymers as synthetic vectors for gene delivery
Phosphorylcholine-polycation diblock copolymers as synthetic vectors for gene delivery
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DOI：
10.1016/j.jconrel.2004.08.028
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发表时间：
2004-11-24
影响因子：
10.8
通讯作者：
Stolnik, S
中科院分区：
文献类型：
--
作者：
Lam, JKW;Ma, Y;Stolnik, S
合成了一种新型的甲基丙烯酸2-（二甲氨基）乙酯-嵌段-2-（甲基丙烯酰氧乙基磷酰胆碱）（DMAEMA-MPC）二嵌段共聚物，并将其作为一种新型的非病毒基因载体进行了研究。这种基于磷酸胆碱（PC）的材料的吸引人的观点是其通过阳离子DMAEMA嵌段有效地缩合DNA的倾向，如先前针对相应的均聚物所证明的，MPC嵌段充当生物相容性空间稳定剂。合成了两个系列的DMAEMA-MPC二嵌段共聚物用于评估，独立地和系统地改变MPC或DMAEMA嵌段长度。根据共聚物的分子组成，观察到显着不同的DNA-共聚物复合物。某些聚合物结构导致形成高度浓缩的、空间稳定的直径为120-140 nm的DNA复合物，而一些聚合物结构导致具有“意大利面条”结构的部分浓缩的DNA-聚合物复合物，表明共聚物组合物对于平衡浓缩和空间稳定效应的重要性。观察到具有优化的物理化学性质的复合物的低水平的非特异性细胞缔合，表明MPC表面层在与生物膜的相互作用中的作用和在防止与体内组织的混杂相互作用中的重要性质，并可能允许在靶向配体的附着后缩合物的细胞特异性递送。(C)2004 Elsevier B. V.保留所有权利。
A novel 2-(dimethylamino)ethyl methacrylate-block-2-(methacryloyloxyethyl phosphorylcholine) (DMAEMA-MPC) diblock copolymer was synthesized and investigated as a new non-viral vector for gene delivery. The attractive perspective of this phosphorylcholine (PC)-based material is its propensity to condense DNA efficiently via the cationic DMAEMA block, as previously demonstrated for the respective homopolymer, with the MPC block acting as a biocompatible steric stabilizer. Two series of DMAEMA-MPC diblock copolymers were synthesized for evaluation, varying independently and systematically either MPC or DMAEMA block length. Markedly different DNA-copolymer complexes were observed depending on the copolymer molecular composition. Certain polymeric structures led to formation of highly condensed, sterically stabilized DNA complexes of 120-140 nm diameter, while some resulted in partly condensed DNA-polymer complexes with 'spaghetti' structures, indicating the importance of a copolymer composition to balance condensing and steric stabilization effect. A low level of non-specific cellular association of the complexes with optimized physicochemical properties was seen, indicating the role of MPC surface layer in the interactions with biological membranes and important property in preventing promiscuous interactions with tissues in the body and potentially allowing for cellular specific delivery of the condensates following the attachment of a targeting ligand. (C) 2004 Elsevier B.V. All rights reserved.