• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Acta biomaterialia >Polycation-detachable nanoparticles self-assembled from mPEG-PCL-g-SS-PDMAEMA for in vitro and in vivo siRNA delivery.
【24h】

Polycation-detachable nanoparticles self-assembled from mPEG-PCL-g-SS-PDMAEMA for in vitro and in vivo siRNA delivery.

机译：聚碳 - 可拆卸纳米颗粒从MPEG-PCL-G-SS-PDMAEMA进行体外和体内siRNA递送来自组装。

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

Long circulation, cell internalization, endosomal escape and small interfering RNA (siRNA) release to the cytoplasm are the prerequisite considerations for siRNA delivery vectors. Herein, a kind of sheddable nanoparticles (NPs) with micelle architecture for siRNA delivery were fabricated by using an intracellular-activated polycation-detachable copolymer (PECssD), which was prepared by introducing highly reducing environment-responsive disulfide linkages between PEGylated polycaprolactone (PCL) and the grafted polycation, poly(2-dimethylaminoethyl methacrylate) (PDMAEMA). The architecture of PECssD self-assembled NPs includes a biodegradable hydrophobic PCL core, a PEG shield and a detachable comb-like polycation surface. The stable nanosized complexes of PECssD NPs with siRNA, termed PECssD/siRNA micelleplexes, were formed, which could prolong circulation, improve accumulation and retention in tumor tissue, and be favorable for internalization. In particular, the cleavage of the disulfide linkages in the intracellular microenvironment and the subsequent dissociation of the PDMAEMA/siRNA polyplexes from the PEGylated PCL cores of PECssD/siRNA micelleplexes were also confirmed, which facilitated the endosomal escape and the efficient release of siRNA. As a result, the distribution of siRNA in cytoplasm was enhanced and subsequently promoted the efficiency of siRNA in gene silencing. Furthermore, systemic administration of the NPs carrying siPlk1 (polo-like kinase 1 specific siRNA) induced a tumor-suppressing effect in the HeLa-Luc xenograft murine model. Therefore, the devised strategy of the polycation-detachable copolymer PECssD NPs could address the requirements of the multistep systemic delivery process of siRNA. The hydrophobic core of the PECssD/siRNA micelleplexes is expected to entrap antitumor drugs or other therapeutic agents for combined therapies.
机译：长循环，细胞内化，内体逃逸和小干扰RNA（siRNA）释放到细胞质上是siRNA递送载体的先决条件考虑因素。这里，通过使用细胞内活化的聚盐可拆卸共聚物（PECSSD）制造具有用于siRNA递送的胶束架构的脱液纳米颗粒（NPS），其通过在聚乙二醇化聚己内酯（PCL）之间的高度还原的环境响应性二硫键键入来制备和接枝的聚阳离子，聚（2-二甲基氨基甲基丙烯酸甲酯）（PDMAEMA）。 PECSSD自组装NPS的结构包括可生物降解的疏水PCL芯，PEG屏蔽和可拆卸的梳状络合表面。形成含有siRNA的PECSD NPS的稳定纳米化络合物，称为PECSSD / siRNA胶束分布，其可以延长循环，改善肿瘤组织中的积累和保留，并有利于内化。特别地，还证实了细胞内微环境中的二硫键和随后从PECSEMA / siRNA核心的PDMAEMA / siRNA多元分开的分离的裂解，这促进了内体逃逸和siRNA的有效释放。结果，提高了细胞质中siRNA的分布，随后促进了基因沉默中siRNA的效率。此外，携带SIPLK1的NPS（POLO样激酶1特异性siRNA）的全身施用诱导Hela-Luc异种移植鼠模型中的肿瘤抑制效果。因此，络合 - 可拆卸共聚物PECSSD NPS的设计策略可以解决siRNA的多步骤全身递送过程的要求。预期PECSSD / siRNA胶合体的疏水核心预期诱捕抗肿瘤药物或其他治疗剂的组合疗法。

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