کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1426274 | 986803 | 2009 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Efficient intracellular siRNA delivery strategy through rapid and simple two steps mixing involving noncovalent post-PEGylation Efficient intracellular siRNA delivery strategy through rapid and simple two steps mixing involving noncovalent post-PEGylation](/preview/png/1426274.png)
Two different and well-defined methacrylate-based (co)polymers were employed as a polymeric siRNA delivery system. siRNA, poly(2-(dimethylamino) ethyl methacrylate) homopolymers (PDMAEMA) and poly(2-(dimethylamino) ethyl methacrylate)-b-poly (ethyleneglycol) α-methoxy, ω-methacrylate (PDMAEMA-b-PMAPEG) palm-tree-like copolymer ternary complexes were prepared using a rapid and simple two-step mixing protocol involving noncovalent post-PEGylation, and physicochemical properties including hydrodynamic diameter, zeta-potential and siRNA condensation efficiency were characterized. Transfection efficiency, intracellular uptake, and cytotoxicity of ternary complexes were also evaluated. Ternary complexes provide efficient condensation and compaction of siRNA within the cationic core of complexes. Noncovalent post-PEGylation provides the ternary complexes with enzymatic and serum stability without harming complex formation and condensation of siRNA. Thereby, under an optimal N/P ratio, ternary complexes exhibited brilliant gene silencing efficiency with low cytotoxicity in media containing 10% serum. Confocal microscopy clearly showed efficient and even intracellular uptake of complexes by cells via endocytosis. This study highlights the excellent properties of noncovalent post-PEGylated ternary complexes produced by rapid and simple mixing. Accordingly, these findings suggest that the formation of ternary complexes could be utilized as a safe and effective polymeric siRNA delivery strategy.
The ternary complexes were efficiently taken up by cells and silenced the target gene expression with low cytotoxicity under conditions involving serum exposure.Fx1Figure optionsDownload as PowerPoint slide
Journal: Journal of Controlled Release - Volume 138, Issue 2, 1 September 2009, Pages 141–147