Biodegradable copolymers with identical cationic segments and their performance in siRNA delivery
Biodegradable copolymers with identical cationic segments and their performance in siRNA delivery
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DOI：
10.1016/j.jconrel.2012.01.015
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发表时间：
2012-04-30
影响因子：
10.8
通讯作者：
Jing, Xiabin
中科院分区：
文献类型：
--
作者：
Qi, Ruogu;Liu, Shi;Jing, Xiabin
可生物降解的阳离子共聚物单甲氧基聚(乙烯-glycol)-block-poly(epsilon-caprolactone)-block-poly(L-lysine))(mpeg-b-pcl-b-pll，进一步缩写为mpeg-b-pcl.通过己内酯和L赖氨酸N-羧酸酐的开环聚合和点击反应，合成了具有不同长度的PCL嵌段和PLL嵌段之间具有三唑键的不同长度的PCL嵌段(如“M”)。与不带PCL嵌段的共聚物(mpeg-b-pll，进一步缩写)。作为对照，研究了这些共聚物与siRNA的自组装和络合作用。进一步考察了P(P-络合物)络合物和M1和M2络合物(M1-络合物和M2-络合物)的siRNA载量、siRNA递送性能和细胞摄取，并与它们的嵌段共聚物组成进行了关联。结果表明，嵌段共聚物P、M1和M2具有较强的结合能力，形成的复合体能够抵抗肝素置换和核糖核酸酶降解。与P-复合体相比，M-复合体具有更小的尺寸和更高的颗粒密度，比游离的siRNA或P-复合体更容易通过内吞作用内化，它们表现出比P-复合体更高的siRNA递送效率和基因沉默效率。胶束复合体的消声效率接近脂质体(TM)2000，远好于PEI-25 kDa。因此，mpeg-b-PCL-b-PLL有望成为一种很有前途的siRNA载体。(C)2012爱思唯尔B.V.保留所有权利。基因传递
The biodegradable cationic copolymers monomethoxy poly(ethylene glycol)-block-poly(epsilon-caprolactone)-block-poly(L-lysine) (mPEG-b-PCL-b-PLL, further abbr. as "M") with a PCL block of different lengths and with a triazole linkage between the PCL and PLL blocks were synthesized via ring-opening polymerization of epsilon-caprolactone and L-lysine N-carboxyanhydride and click reactions. With the copolymer without the PCL block (mPEG-b-PLL, further abbr. as "P") as a control, self-assembling and complexation of these copolymers with siRNA were studied. siRNA-loading capacity, siRNA delivery performance and cellular uptake of the complexation products, namely complex from P (P-complex) and complexes from M1 and M2 (M1-complex and M2-complex), were further examined and correlated to their block-copolymer compositions. The results showed the block copolymers P, M1 and M2 have strong enough binding ability so that the complexes formed can resist the heparin displacement and RNase degradation. Compared to P-complex, M-complexes have smaller size and higher particle density so that they can be internalized via endocytosis more easily than free siRNA or P-complex and they display higher siRNA delivery efficiency and higher gene silencing efficiency than P-complex. The silencing efficiency of micellar complex is close to that of Lipofectamine (TM) 2000 and much better than PEI-25 kDa. Therefore, mPEG-b-PCL-b-PLL is expected to be a promising siRNA carrier. (C) 2012 Elsevier B.V. All rights reserved. GENE DELIVERY