Peptide-functionalized nanogels for targeted siRNA delivery.
Peptide-functionalized nanogels for targeted siRNA delivery.
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DOI：
10.1021/bc800547c
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发表时间：
2009-05-20
影响因子：
4.7
通讯作者：
Lyon LA
中科院分区：
文献类型：
--
作者：
Blackburn WH;Dickerson EB;Smith MH;McDonald JF;Lyon LA
siRNA疗法开发中的主要瓶颈是其递送至所需细胞类型或组织，随后有效穿过细胞膜，随后使靶向mRNA沉默。为了解决这个问题，我们描述了核/壳水凝胶纳米颗粒（纳米凝胶）的合成与表面定位的肽，特异性靶向卵巢癌细胞系具有高表达水平的Eph 2A受体。这些纳米凝胶也被证明在siRNA的非共价包封中是高度有效的，并且能够在含血清的介质中细胞特异性地递送寡核苷酸。细胞毒性和活力测定揭示，纳米凝胶构建体在所研究的条件下是无毒的，因为在递送后没有观察到毒性或细胞增殖的降低。重要的是，基因沉默的初步研究表明，纳米凝胶介导的靶向EGF受体的siRNA递送导致该受体的敲低。这些结果表明，在纳米凝胶的内体摄取和内体逃逸过程中siRNA具有优异的保护作用，因为基因沉默需要细胞溶质中的siRNA活性。
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.
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影响因子：
2.9
作者：
Mok, Hyejung;Park, Tae Gwan
通讯作者：
Park, Tae Gwan
影响因子：
4.7
作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Farokhzad, Omid C.
影响因子：
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作者：
Larsen, Alice Bjerregaard;Pedersen, Mikkel Wandahl;Poulsen, Hans Skovgaard
通讯作者：
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