Double Click-Functionalized siRNA Polyplexes for Gene Silencing in Epidermal Growth Factor Receptor-Positive Tumor Cells,ACS Biomaterials Science & Engineering

当前位置： X-MOL 学术 › ACS Biomater. Sci. Eng. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Double Click-Functionalized siRNA Polyplexes for Gene Silencing in Epidermal Growth Factor Receptor-Positive Tumor Cells
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2020-01-09 , DOI: 10.1021/acsbiomaterials.9b01904
Yanfang Wang ₁ , Jie Luo ₁ , Ines Truebenbach ₁ , Sören Reinhard ₁ , Philipp Michael Klein ₁ , Miriam Höhn ₁ , Sarah Kern ₁ , Stephan Morys ₁ , Dominik M. Loy ₁ , Ernst Wagner _{1,

2} , Wei Zhang ₁

Affiliation

Sequence-defined lipo-oligomers generated via solid-phase assisted synthesis have been developed as siRNA delivery systems for RNA-interference (RNAi) based gene silencing. Here, novel siRNA lipo-polyplexes were established, which were postmodified with monovalent or bivalent DBCO-PEG₂₄ agents terminated with peptide GE11 (YHWYGYTPQNVI) for epidermal growth factor receptor (EGFR)-targeted siRNA delivery into EGFR-positive tumor cells. Lipo-oligomers containing eight cationizable succinoyltetraethylene-pentamine (Stp) units mediated higher siRNA nanoparticle core stability than those containing four Stp units, and the incorporation of histidines for enhanced endosomal buffer capacity resulted in an improved gene silencing efficiency. Lipo-polyplexes modified with monovalent or bivalent PEG-GE11 via the copper-free click reaction possessed significantly enhanced cellular internalization and transfection efficiency in EGF receptor-positive human cervical KB and hepatoma Huh7 cells in comparison with the corresponding lipo-polyplexes shielded with PEG₂₄ without targeting. Furthermore, modification with the bivalent DBCO-PEG₂₄-GE11 ligand resulted in higher gene silencing efficiency than modification with the same equivalents of the monovalent DBCO-PEG₂₄-GE11 ligand.

中文翻译：

双击功能的siRNA复合物在表皮生长因子受体阳性肿瘤细胞中的基因沉默

已经开发了通过固相辅助合成生成的序列定义的脂质寡聚体，作为用于基于RNA干扰（RNAi）的基因沉默的siRNA传递系统。在这里，建立了新的siRNA脂质多聚体，将其用单价或二价DBCO-PEG ₂₄后修饰以肽GE11（YHWYGYTPQNVI）终止的药物，可将表皮生长因子受体（EGFR）靶向的siRNA输送到EGFR阳性肿瘤细胞中。包含八个可阳离子化的琥珀酰四亚乙基五胺（Stp）单元的脂质寡聚体比包含四个Stp单元的脂质寡聚体介导了更高的siRNA纳米颗粒核心稳定性，并且为了增强内体缓冲液容量而掺入组氨酸导致基因沉默效率提高。与通过PEG ₂₄保护的相应脂多聚体相比，经单价或二价PEG-GE11通过无铜点击反应修饰的脂多聚体在EGF受体阳性的人宫颈癌KB和肝癌Huh7细胞中具有显着增强的细胞内在化和转染效率。没有定位。此外，与用相同当量的单价DBCO-PEG ₂₄ -GE11配体进行修饰相比，用二价DBCO-PEG ₂₄ -GE11配体进行修饰导致更高的基因沉默效率。

更新日期：2020-01-09

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11