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通过β-环糊精核的原子转移自由基聚合制备多臂阳离子星聚合物:支化度和臂长对基因传递的影响。

Multiarm cationic star polymers by atom transfer radical polymerization from β-cyclodextrin cores: influence of arm number and length on gene delivery.

机构信息

State Key Laboratory of Chemical Resource Engineering, Ministry of Education, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, People's Republic of China.

出版信息

Acta Biomater. 2013 Jan;9(1):4726-33. doi: 10.1016/j.actbio.2012.08.020. Epub 2012 Aug 20.

Abstract

Controlled β-cyclodextrin (β-CD) core-based cationic star polymers have attracted considerable attention as non-viral gene carriers. Atom transfer radical polymerization (ATRP) could be readily used to produce the star-shaped polymers. The precise control of the number of initiation sites on the multifunctional core was of crucial importance to the investigation of the structure-property relationship of the functional star gene carriers. Herein, the controlled multiarm star polymers consisting of a β-CD core and various arm lengths of poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) were prepared via ATRP from the chloroacetylated β-CD with well-designed initiation sites. Generally, these star polycations can condense plasmid DNA into 100-150 nm nanoparticles with positive zeta potentials of 30-40 mV at N/P ratios (star polymer to DNA ratios) of 17 or higher. The effects of arm numbers and lengths on gene delivery were investigated in detail. With a fixed length of the PDMAEMA arm, the fewer the number of arms, the lower the toxicity. The star polycations with suitable arm numbers possess the best transfection ability. On the other hand, with the fixed molecular weights, the shorter the arms, the lower the toxicity. The polymers with 21 arms possess the lowest transfection efficiency.

摘要

作为非病毒基因载体,受控制的β-环糊精(β-CD)核阳离子星形聚合物引起了相当大的关注。原子转移自由基聚合(ATRP)可用于制备星形聚合物。多功能核上引发位点的数量的精确控制对于功能性星形基因载体的结构-性能关系的研究至关重要。在此,通过 ATRP 从具有精心设计的引发位点的氯乙酰化β-CD 制备了由β-CD 核和不同臂长的聚(2-(二甲氨基)乙基甲基丙烯酸酯)(PDMAEMA)组成的受控多臂星形聚合物。通常,这些星型聚阳离子在 N/P 比(星形聚合物与 DNA 的比)为 17 或更高时,可以将质粒 DNA 凝聚成 100-150nm 的纳米颗粒,其正zeta 电位为 30-40mV。详细研究了臂数和长度对基因传递的影响。在 PDMAEMA 臂长度固定的情况下,臂数越少,毒性越低。具有合适臂数的星型聚阳离子具有最佳的转染能力。另一方面,在固定分子量的情况下,臂越短,毒性越低。具有 21 个臂的聚合物具有最低的转染效率。

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