Fully synthetic polymer vesicles for intracellular delivery of antibodies in live cells
Fully synthetic polymer vesicles for intracellular delivery of antibodies in live cells
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DOI：
10.1096/fj.12-212183
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发表时间：
2013-01-01
期刊：
影响因子：
4.8
通讯作者：
Battaglia, Giuseppe
中科院分区：
文献类型：
--
作者：
Canton, Irene;Massignani, Marzia;Battaglia, Giuseppe
在药理学和生物医学工业中，都出现了开发靶向细胞内机制的新工具的需求。在细胞内有效递送功能活性蛋白质可能是一种强大的研究策略，特别是通过使用抗体。在这项工作中，我们报告了一种纳米载体，用于将抗体有效地包封和递送到活细胞中，而不会显著损失细胞活力或对细胞代谢活性产生任何有害影响。该递送系统基于聚[2-（甲基丙烯酰氧基）乙基磷酸胆碱]-嵌段-[2-（二异丙基氨基）乙基甲基丙烯酸酯]（PMPC-PDPA），其是一种pH敏感的二嵌段共聚物，其在生理pH下自组装以形成纳米尺寸的囊泡，也称为聚合物囊泡。聚合物囊泡可以在不同类型的活细胞内成功地递送相对高的抗体有效载荷。我们证明，这些抗体可以靶向其各自的表位显示免疫标记的γ-微管蛋白，肌动蛋白，高尔基体蛋白，和转录因子NF-κ B在活细胞中。最后，我们证明了抗体的细胞内递送可以控制特定的亚细胞事件，以及调节细胞活性和促炎过程。坎顿岛，Massignani，M.，Patikarnmonthon，N.，基耶里科湖Robertson，J.，Renshaw，S.一、Warren，N. J.，Madsen，J.P.，Armes，S P.，刘易斯，A. L.，巴塔利亚湾用于活细胞中抗体细胞内递送的全合成聚合物囊泡。FASEB J.27，98-108（2013）. www.fasebj.org
There is an emerging need both in pharmacology and within the biomedical industry to develop new tools to target intracellular mechanisms. The efficient delivery of functionally active proteins within cells is potentially a powerful research strategy, especially through the use of antibodies. In this work, we report on a nanovector for the efficient encapsulation and delivery of antibodies into live cells with no significant loss of cell viability or any deleterious effect on cell metabolic activity. This delivery system is based on poly[2-(methacryloyloxy) ethyl phosphorylcholine]-block-[2-(diisopropylamino) ethyl methacrylate] (PMPC-PDPA), a pH-sensitive diblock copolymer that self-assembles to form nanometer-sized vesicles, also known as polymersomes, at physiological pH. Polymersomes can successfully deliver relatively high antibody payloads within different types of live cells. We demonstrate that these antibodies can target their respective epitope showing immunolabeling of gamma-tubulin, actin, Golgi protein, and the transcription factor NF-kappa B in live cells. Finally, we demonstrate that intracellular delivery of antibodies can control specific subcellular events, as well as modulate cell activity and proinflammatory processes.-Canton, I., Massignani, M., Patikarnmonthon, N., Chierico, L., Robertson, J., Renshaw, S. A., Warren, N. J., Madsen, J. P., Armes, S P., Lewis, A. L., Battaglia, G. Fully synthetic polymer vesicles for intracellular delivery of antibodies in live cells. FASEB J. 27, 98-108 (2013). www.fasebj.org