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首页> 外文期刊>Biotechnology Progress >Multifunctional siRNA Delivery System: Polyelectrolyte Complex Micelles of Six-arm PEG Conjugate of siRNA and Cell Penetrating Peptide with Crosslinked Fusogenic Peptide
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Multifunctional siRNA Delivery System: Polyelectrolyte Complex Micelles of Six-arm PEG Conjugate of siRNA and Cell Penetrating Peptide with Crosslinked Fusogenic Peptide

机译：多功能siRNA输送系统：六臂PEG siRNA和细胞穿透肽与交联融合肽的共轭聚电解质复合胶束

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摘要

For therapeutic applications of small interfering RNA (siRNA), serum stability, enhanced cellular uptake, and facile endosome escape are key issues for designing carriers. In this study, green fluorescent protein (GFP) siRNA was conjugated to a six-arm polyethylene glycol (PEG) derivative via a reducible disulfide linkage (6PEG-siRNA). The 6PEG-siRNA conjugate was also functionalized with a cell penetrating peptide, Hph1 to enhance its cellular uptake property (6PEG-siRNA-Hph1. The 6PEG-siRNA-Hph1 conjugate was electrostatically complexed with cationic self-crosslinked fusogenic KALA peptide (cl-KALA) to form multifunctional polyelectrolyte complex micelles for gene silencing. The resultant siRNA complex formulation with multiple PEG chains showed superior physical stability and resistance to enzymatic degradation. The 6PEG-siRNA-Hph1/cl-KALA complexes exhibited enhanced GFP gene silencing efficiency for MDA-MB-435 cells in the serum containing condition. The current reducible and multifunctional polyelectrolyte complex micelles are expected to have high potential for efficient delivery of therapeutic siRNA.
机译：对于小干扰RNA（siRNA）的治疗应用而言，血清稳定性，增强的细胞摄取和便捷的核内体逃逸是设计载体的关键问题。在这项研究中，绿色荧光蛋白（GFP）siRNA通过可还原的二硫键（6PEG-siRNA）与六臂聚乙二醇（PEG）衍生物偶联。 6PEG-siRNA偶联物还可以通过细胞穿透肽Hph1功能化以增强其细胞摄取特性（6PEG-siRNA-Hph1。6PEG-siRNA-Hph1偶联物与阳离子自交联融合KALA肽（cl-KALA ）形成多功能聚电解质复合物胶束以沉默基因，所得具有多条PEG链的siRNA配合物制剂具有优异的物理稳定性和对酶促降解的抵抗力; 6PEG-siRNA-Hph1 / cl-KALA复合物显示出增强的GFP基因对MDA-的沉默效率血清中含有MB-435细胞，目前可还原的多功能聚电解质复合胶束有望具有高效递送治疗性siRNA的潜力。

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