Direct delivery of functional proteins and enzymes to the cytosol using nanoparticle-stabilized nanocapsules.
Direct delivery of functional proteins and enzymes to the cytosol using nanoparticle-stabilized nanocapsules.
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DOI：
10.1021/nn402753y
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发表时间：
2013-08-27
期刊：
影响因子：
17.1
通讯作者：
Rotello, Vincent M.
中科院分区：
文献类型：
--
作者：
Tang, Rui;Kim, Chang Soo;Solfiell, David J.;Rana, Subinoy;Mout, Rubul;Velazquez-Delgado, Elih M.;Chompoosor, Apiwat;Jeong, Youngdo;Yan, Bo;Zhu, Zheng-Jiang;Kim, Chaekyu;Hardy, Jeanne A.;Rotello, Vincent M.
关键词：
细胞内蛋白质递送是治疗和基础应用的重要工具。有效的蛋白质递送面临两个主要挑战：有效的细胞摄取和避免内体螯合。在这里，我们报告了一个一般的战略，直接交付的功能蛋白质的胞质溶胶使用纳米粒子稳定的胶囊（NPSC）。这些NPSC通过纳米颗粒、蛋白质货物和脂肪酸胶囊内部之间的超分子相互作用形成和稳定。NPSC直径约为130 nm，具有低毒性和在血清中的优异稳定性。这些NPSC作为治疗性蛋白质载体的有效性通过将全功能的半胱天冬酶-3递送至HeLa细胞并伴随细胞凋亡来证明。绿色荧光蛋白（GFP）的类似递送证实了胞质递送以及所递送蛋白的细胞内靶向，证明了该系统用于治疗和成像应用的实用性。
Intracellular protein delivery is an important tool for both therapeutic and fundamental applications. Effective protein delivery faces two major challenges: efficient cellular uptake and avoiding endosomal sequestration. We report here a general strategy for direct delivery of functional proteins to the cytosol using nanoparticle-stabilized capsules (NPSCs). These NPSCs are formed and stabilized through supramolecular interactions between the nanoparticle, the protein cargo, and the fatty acid capsule interior. The NPSCs are ~130 nm in diameter and feature low toxicity and excellent stability in serum. The effectiveness of these NPSCs as therapeutic protein carriers was demonstrated through the delivery of fully functional caspase-3 to HeLa cells with concomitant apoptosis. Analogous delivery of green fluorescent protein (GFP) confirmed cytosolic delivery as well as intracellular targeting of the delivered protein, demonstrating the utility of the system for both therapeutic and imaging applications.
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