• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Acta biomaterialia >Contribution of hydrophobic/hydrophilic modification on cationic chains of poly(ε-caprolactone)-graft-poly(dimethylamino ethylmethacrylate) amphiphilic co-polymer in gene delivery.
【24h】

Contribution of hydrophobic/hydrophilic modification on cationic chains of poly(ε-caprolactone)-graft-poly(dimethylamino ethylmethacrylate) amphiphilic co-polymer in gene delivery.

机译：疏水/亲水修饰对聚（ε-己内酯）-接枝-聚（二甲基氨基乙基甲基丙烯酸甲酯）两亲共聚物阳离子链在基因传递中的贡献。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Nanoparticles (NPs) assembled from amphiphilic polycations have been certified as potential carriers for gene delivery. Structural modification of polycation moieties may be an efficient route to further enhance gene delivery efficiency. In this study two electroneutral monomers with different hydrophobicities, 2-hydroxyethyl methacrylate (HEMA) and 2-hydroxyethyl acrylate (HEA), were incorporated into the cationic poly(dimethylamino ethyl methacrylate) (PDMAEMA) side-chains of amphiphilic poly(ε-caprolactone)-graft-poly(dimethylamino ethylmethacrylate) (PCD) by random co-polymerization, to obtain poly(ε-caprolactone)-graft-poly(dimethylamino ethyl methacrylate-co-2-hydroxyethyl methacrylate) (PCD-HEMA) and poly(ε-caprolactone)-graft-poly(dimethylamino ethyl methacrylate-co-2-hydroxyethyl acrylate) (PCD-HEA). Minimal HEA or HEMA moieties in PDMAEMA do not lead to statistically significant changes in particle size, zeta potential, DNA condensation properties and buffering capacity of the naked NPs. However, the incorporation of HEMA and HEA lead to reductions and increases, respectively, in the surface hydrophilicity of the naked NPs and NPs/DNA complexes, which was confirmed by water contact angle assay. These simple modifications of PDMAEMA with HEA and HEMA moieties significantly affect the gene transfection efficiency on HeLa cells in vitro: PCD-HEMA NP/DNA complexes show a much higher transfection efficiency than PCD NPs/DNA complexes, while PCD-HEA NPs/DNA complexes show a lower transfection efficiency than PCD NP/DNA complexes. Fluorescence activated cell sorter and confocal laser scanning microscope results indicate that the incorporation of hydrophobic HEMA moieties facilitates an enhancement in both cellular uptake and endosomal/lysosomal escape, leading to a higher transfection efficiency. Moreover, the process of endosomal/lysosomal escape confirmed in our research that PCD and its derivatives do not just rely on the proton sponge mechanism, but also on membrane damage due to the polycation chains, especially hydrophobic modified ones. Hence, it is proved that hydrophobic modification of cationic side-chains is a crucial route to improve gene transfection mediated by polycation NPs.
机译：由两亲性聚阳离子组装而成的纳米粒子（NPs）已被证明是基因传递的潜在载体。聚阳离子部分的结构修饰可能是进一步提高基因递送效率的有效途径。在这项研究中，将具有不同疏水性的两种电子中性单体，甲基丙烯酸2-羟乙酯（HEMA）和丙烯酸2-羟乙酯（HEA）引入到两亲性聚ε-己内酯的阳离子聚甲基丙烯酸二甲氨基乙酯（PDMAEMA）侧链中）通过无规共聚接枝聚（甲基丙烯酸二甲氨基乙基酯）（PCD），得到聚（ε-己内酯）-聚（甲基丙烯酸二甲氨基乙基酯-甲基丙烯酸-2-羟乙酯）（PCD-HEMA）和聚（ ε-己内酯）-接枝-聚（甲基丙烯酸二甲基氨基乙基酯-丙烯酸丙烯酸-2-羟基乙酯）（PCD-HEA）。 PDMAEMA中最小的HEA或HEMA部分不会导致裸露NP的粒径，ζ电位，DNA缩合特性和缓冲能力具有统计学上的显着变化。然而，HEMA和HEA的引入分别导致裸露的NP和NP / DNA复合物的表面亲水性降低和增加，这已通过水接触角分析得到了证实。用HEA和HEMA部分对PDMAEMA进行的这些简单修饰会显着影响体外HeLa细胞上的基因转染效率：PCD-HEMA NP / DNA复合物的转染效率比PCD NP / DNA复合物高得多，而PCD-HEA NP / DNA复合物与PCD NP / DNA复合物相比，显示出较低的转染效率。荧光激活细胞分选仪和共聚焦激光扫描显微镜结果表明，疏水性HEMA部分的引入促进了细胞摄取和内体/溶酶体逸出的增强，从而提高了转染效率。此外，我们的研究证实了内体/溶酶体逸出的过程表明，PCD及其衍生物不仅依赖于质子海绵的机理，而且还依赖于聚阳离子链（尤其是疏水性修饰的链）造成的膜损伤。因此，证明阳离子侧链的疏水修饰是改善由聚阳离子NP介导的基因转染的关键途径。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号