Guanidine-Containing Methacrylamide (Co)polymers via aRAFT: Toward a Cell Penetrating Peptide Mimic().
Guanidine-Containing Methacrylamide (Co)polymers via aRAFT: Toward a Cell Penetrating Peptide Mimic().
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DOI：
10.1021/mz200012p
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发表时间：
2012-01-17
影响因子：
7.015
通讯作者：
McCormick CL
中科院分区：
文献类型：
--
作者：
Treat NJ;Smith D;Teng C;Flores JD;Abel BA;York AW;Huang F;McCormick CL
本文报道了3-胍基丙基甲基丙烯酰胺（GPMA）的水相可逆加成-断裂链转移（aRAFT）聚合合成和控制自由基同链和嵌段共聚。制备了N-（2-羟丙基）甲基丙烯酰胺（HPMA）的均聚物和嵌段共聚物，以模拟细胞穿透肽（CPPs）和聚精氨酸（bbb6单位）的行为，这些行为已被证明可以穿过细胞膜。4-氰基-4-（乙基磺酰硫代羰基磺酰）戊酸（CEP）在缓冲液中的均聚反应具有准一级动力学，分子量随转化率呈线性增长。通过GPMA macroCTA的成功链延伸，得到GPMA37-b-GPMA61 (Mw/Mn =1.05)，证明了“活”硫碳基硫ω端基的保留。合成了GPMA与非免疫原性、生物相容性HPMA的嵌段共聚物，产物为HPMA271-b-GPMA13 （Mw/Mn = 1.15）。值得注意的是，利用fitc标记的含gpma的共聚物，在4°C和37°C下与KB细胞孵生2.5 h后，通过荧光显微镜、共聚焦激光扫描显微镜和流式细胞术实验证实了细胞内摄取。观察到的细胞摄取设施和aRAFT聚合提供的结构控制表明，这些合成（co）聚合物作为靶向治疗药物递送载体的巨大潜力。
We report the synthesis and controlled radical homo- and block copolymerization of 3-guanidinopropyl methacrylamide (GPMA) utilizing aqueous reversible addition-fragmentation chain transfer (aRAFT) polymerization. The resulting homopolymer and block copolymer with N-(2-hydroxypropyl) methacrylamide (HPMA) were prepared to mimic the behavior of cell penetrating peptides (CPPs) and poly(arginine) (> 6 units) which have been shown to cross cell membranes. The homopolymerization mediated by 4-cyano-4-(ethylsulfanylthiocarbonylsulfanyl)pentanoic acid (CEP) in aqueous buffer exhibited pseudo-first-order kinetics and linear growth of molecular weight with conversion. Retention of the “living” thiocarbonylthio ω-end-group was demonstrated through successful chain extension of the GPMA macroCTA yielding GPMA37-b-GPMA61 (Mw/Mn =1.05). Block copolymers of GPMA with the non-immunogenic, biocompatible HPMA were synthesized yielding HPMA271-b-GPMA13 (Mw/Mn = 1.15). Notably, intracellular uptake was confirmed by fluorescence microscopy, confocal laser scanning microscopy, and flow cytometry experiments after 2.5 h incubation with KB cells at 4 °C and at 37 °C utilizing FITC-labeled, GPMA-containing copolymers. The observed facility of cellular uptake and the structural control afforded by aRAFT polymerization suggest significant potential for these synthetic (co)polymers as drug delivery vehicles in targeted therapies.
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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：
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作者：
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DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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