Peptide-Functionalized Nanogels for Targeted siRNA Delivery

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• 作者：William H. Blackburn ; Erin B. Dickerson ; Michael H. Smith ; John F. McDonald ; L. Andrew Lyon
• 刊名：Bioconjugate Chemistry
• 出版年：2009
• 出版时间：May 20, 2009
• 年：2009
• 卷：20
• 期：5
• 页码：960-968
• 全文大小：237K
• 年卷期：v.20,no.5(May 20, 2009)
• ISSN：1520-4812

文摘

A major bottleneck in the development of siRNA therapies is their delivery to the desired cell type or tissue, followed by effective passage across the cell membrane with subsequent silencing of the targeted mRNA. To address this problem, we describe the synthesis of core/shell hydrogel nanoparticles (nanogels) with surface-localized peptides that specifically target ovarian carcinoma cell lines possessing high expression levels of the Eph2A receptor. These nanogels are also demonstrated to be highly effective in the noncovalent encapsulation of siRNA and enable cell-specific delivery of the oligonucleotides in serum-containing medium. Cell toxicity and viability assays reveal that the nanogel construct is nontoxic under the conditions studied, as no toxicity or decrease in cell proliferation is observed following delivery. Importantly, a preliminary investigation of gene silencing illustrates that nanogel-mediated delivery of siRNA targeted to the EGF receptor results in knockdown of that receptor. Excellent protection of siRNA during endosomal uptake and endosomal escape of the nanogels is suggested by these results since siRNA activity in the cytosol is required for gene silencing.