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Responsive pentablock copolymers for siRNA delivery

机译：响应于siRNA递送的响应偏心锁共聚物

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摘要

In this study, temperature and pH responsive cationic and amphiphilic pentablock copolymers, which consist of the temperature responsive triblock Pluronic F127 sandwiched between pH responsive PDEAEM (poly(2-diethylaminoethyl methacrylate)) end blocks, were used for the first time in the development of polyplex and gold nanoparticle (AuNP) based multicomponent siRNA delivery systems (MCSs). Copolymers in both systems protected siRNA from external effects, provided cell entry and endosomal escape. The thermoreversible micellization of the hydrophobic PPO block facilitated the cellular entry while the PDEAEM blocks enhanced the endosomal escape through protonated tertiary amine groups by pH buffering. The synergistic advantages of the different blocks showed an enhanced effect in the MCSs due to attachment and surface configuration reasons. The siRNA transfection efficiency of MCSs against luciferase expressing SKOV3 cells was 15% higher than both the polyplexes alone and the commercial siRNA transfection agent Lipofectamine RNAiMax at the same applied dose, without any toxicity. The results indicated that the multicomponent systems based on the responsive cationic pentablock copolymers and gold nanoparticles have promising potential as an efficient siRNA delivery vector for future applications.
机译：在该研究中，温度和pH响应阳离子和两亲硅基五硅聚糖组成，其由夹在pH响应Pderem（聚（2-二乙基氨基甲基丙烯酸酯））端嵌段之间夹在的温度响应性三嵌段Pluronic F127，首次使用基于多分布和金纳米粒子（AUNP）的多组分siRNA递送系统（MCS）。两种系统中的共聚物保护来自外部效应的siRNA，提供了细胞入口和内体逸出。疏水性PPO嵌段的热可逆胶束促进了细胞进入，同时PDEAEM块通过pH缓冲通过质子化的叔胺基团增强了内体逸出。由于附着和表面配置原因，不同块的协同优点显示了MCS中的增强效果。对表达SkoV3细胞的荧光素酶的MCSS的siRNA转染效率比单独的多单双药物高15％，并且商业siRNA转染剂Lipofectamine Rnaimax在同一施用剂量的情况下，没有任何毒性。结果表明，基于响应性阳离子Pentablock共聚物和金纳米颗粒的多组分系统具有有效的潜力作为未来应用的有效siRNA递送载体。

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  • 来源
    《RSC Advances》 |2015年第54期|共13页
  • 作者

    Uz Metin; Mallapragada Surya K.; Altinkaya Sacide Alsoy;

  • 作者单位

    Izmir Inst Technol Dept Chem Engn TR-35430 Izmir Turkey;

    Iowa State Univ Dept Chem &

    Biol Engn Ames IA 50011 USA;

    Izmir Inst Technol Dept Chem Engn TR-35430 Izmir Turkey;

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  • 正文语种 eng
  • 中图分类 化学;
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