Self-Assembly of Peptides into Spherical Nanoparticles for Delivery of Hydrophilic Moieties to the Cytosol
Self-Assembly of Peptides into Spherical Nanoparticles for Delivery of Hydrophilic Moieties to the Cytosol
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DOI：
10.1021/nn901414q
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发表时间：
2010-05-01
期刊：
影响因子：
17.1
通讯作者：
Fabre, John W.
中科院分区：
文献类型：
--
作者：
Collins, Louise;Parker, Alan L.;Fabre, John W.
我们报道了一类新型的自组装肽纳米颗粒，通过混合K-16肽和净电荷为-5的20个氨基酸的肽（GLFEALLELLESLWELLLEA）的水溶液形成。颗粒形成是盐依赖性的，并产生直径类似于120至类似于800 nm的完美球形纳米颗粒，这取决于缓冲液组成和温度，对于阳离子和阴离子肽，化学计量类似于1：2.5。阴离子肽在水溶液中形成α-螺旋，在螺旋的一侧具有所有五个谷氨酸，并且完全作为9-10个肽的离散寡聚体存在。具有45-50负性的刚性寡聚体几乎肯定代表这些纳米颗粒的核心组分，通过静电与非结构化K-16肽结合在一起。细胞通过内吞过程内化这些颗粒，并且游离颗粒经常在胞质溶胶中看到，这可能是因为阴离子肽的酸依赖性融合特性。在其他应用中，这些颗粒具有将单个或多个治疗部分直接靶向递送至胞质溶胶的潜力，并且我们报告了K-16连接的促凋亡肽的成功递送。
We report a novel class of self-assembling peptide nanoparticles formed by mixing aqueous solutions of K-16 peptide and a 20 amino acid peptide of net charge -5 (GLFEALLELLESLWELLLEA). Particle formation is salt-dependent and yields perfectly spherical nanoparticles of similar to 120 to similar to 800 nm diameter, depending on buffer composition and temperature, with a stoichiometry of similar to 1:2.5 for the cationic and anionic peptides. The anionic peptide forms an cc-helix in aqueous solution, has all five glutamates on one side of the helix, and exists entirely as a discrete oligomer of 9-10 peptides. A rigid oligomer with 45-50 negative almost certainly represents the core component of these nanoparticles, held together by electrostatic with the unstructured K-16 peptide. Cells internalize these particles by an endocytic process, and free particles are frequently seen in the cytosol, presumably because of the acid-dependent fusogenic properties of the anionic peptide. Among other applications, these particles have potential for the targeted delivery of single or multiple therapeutic moieties directly to the cytosol, and we report the successful delivery of a K-16-linked pro-apoptosis peptide.