Facile synthesis of multivalent folate-block copolymer conjugates via aqueous RAFT polymerization: targeted delivery of siRNA and subsequent gene suppression.
Facile synthesis of multivalent folate-block copolymer conjugates via aqueous RAFT polymerization: targeted delivery of siRNA and subsequent gene suppression.
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DOI：
10.1021/bm8014768
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发表时间：
2009-04-13
影响因子：
6.2
通讯作者：
McCormick, Charles L.
中科院分区：
文献类型：
--
作者：
York, Adam W.;Zhang, Yilin;Holley, Andrew C.;Guo, Yanlin;Huang, Faqing;McCormick, Charles L.
报道了使用定义明确的多价叶酸偶联嵌段共聚物的小干扰核糖核酸（siRNA）的细胞特异性递送。通过水相可逆加成-断裂链转移（RAFT）聚合合成了具有生物相容性的伯胺功能性嵌段阳离子共聚物。用永久亲水性单体N-（2-羟丙基）甲基丙烯酰胺（HPMA）与含伯胺单体N-（3-氨丙基）甲基丙烯酰胺（APMA）共聚。聚（HPMA）赋予生物相容性，而APMA提供允许叶酸衍生物缀合的胺官能团。用阳离子嵌段聚（N-[3-（二甲基氨基）丙基]甲基丙烯酰胺）使共聚物（HPMA-stat-APMA）扩链，以促进共聚物与siRNA的带负电荷的磷酸骨架之间的静电络合。值得注意的是，聚（HPMA）使中性复合物在水溶液中稳定，而APMA允许靶向部分的缀合，因此，双重规避了与经由阳离子带电复合物递送基因（通用转染）相关的问题。荧光显微镜和基因下调研究表明，这些中性复合物可以特异性地传递到过表达叶酸受体的癌细胞。
Cell specific delivery of small interfering ribonucleic acid (siRNA) using well-defined multivalent folate-conjugated block copolymers is reported. Primary amine functional, biocompatible, hydrophilic-block-cationic copolymers were synthesized via aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization. N-(2-hydroxypropyl)methacrylamide) (HPMA), a permanently hydrophilic monomer, was copolymerized with a primary amine containing monomer, N-(3-aminopropyl)methacrylamide (APMA). Poly(HPMA) confers biocompatibility while APMA provides amine functionality allowing conjugation of folate derivatives. (HPMA-stat-APMA) was chain extended with a cationic block, poly(N-[3-(dimethylamino)propyl]methacrylamide) in order to promote electrostatic complexation between the copolymer and the negatively charged phosphate backbone of siRNA. Notably, poly(HPMA) stabilizes the neutral complexes in aqueous solution while APMA allows the conjugation of a targeting moiety, thus, dually circumventing problems associated with the delivery of genes via cationically charged complexes (universal transfection). Fluorescence microscopy and gene down-regulation studies indicate that these neutral complexes can be specifically delivered to cancer cells that over-express folate receptors.
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DOI：
10.1016/j.jconrel.2008.10.004
发表时间：
2009-02-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Convertine AJ;Benoit DS;Duvall CL;Hoffman AS;Stayton PS
通讯作者：
Stayton PS
影响因子：
10.8
作者：
Lam, JKW;Ma, Y;Stolnik, S
通讯作者：
Stolnik, S
影响因子：
5.1
作者：
Dash, PR;Read, ML;Seymour, LW
通讯作者：
Seymour, LW
影响因子：
4.7
作者：
Bae, Younsoo;Nishiyama, Nobuhiro;Kataoka, Kazunori
通讯作者：
Kataoka, Kazunori
影响因子：
2.9
作者：
Braasch, DA;Jensen, S;Corey, DR
通讯作者：
Corey, DR