超分子β-Sheets稳定蛋白纳米载体用于药物递送和基因转染,ACS Nano

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超分子β-Sheets稳定蛋白纳米载体用于药物递送和基因转染
ACS Nano ( IF 15.8 ) Pub Date : 2017-04-19 00:00:00 , DOI: 10.1021/acsnano.6b08393
Yuan Ping _{1,

2} , Dawei Ding _{1,

2} , Ricardo A. N. S. Ramos _{1,

2} , Harini Mohanram _{1,

2} , Kanagavel Deepankumar _{1,

2} , Jianqing Gao ₃ , Guping Tang ₄ , Ali Miserez _{1,

2}

Affiliation

最近在鱿鱼的吸盘齿中发现的Suckerin蛋白代表了一个有前途的结构生物大分子家族，可以形成由纳米约束的β-折叠层稳定的超分子网络。利用此功能以及它们的特定氨基酸组成，我们证明了人造suckerin-19（S-19）可以被工程化为纳米载体，以在体外和体内有效地进行药物递送和基因转染。首先，我们证明S-19可自组装成β-片状稳定的纳米粒子，其粒径可控制在100-200 nm之间，能够包裹疏水性药物以实现体外pH依赖性释放，并能有效抑制体内肿瘤的生长。我们还表明S-19可以复合和稳定质粒DNA，复合物通过β-sheet结构域的疏水相互作用而稳定，这与阳离子聚合物通常实现的静电相互作用相反，从而降低了细胞毒性。S-19的组氨酸升高含量似乎是由质子海绵效应触发内体逃逸的关键，从而确保既高效基因转染体外和体内。我们的研究表明，S-19代表了一种有前途的功能性蛋白质纳米载体，可用于各种药物和基因递送应用。

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Supramolecular β-Sheets Stabilized Protein Nanocarriers for Drug Delivery and Gene Transfection

Suckerin proteins, recently discovered in the sucker ring teeth of squids, represent a family of promising structural biomacromolecules that can form supramolecular networks stabilized by nanoconfined β-sheets. Exploiting this feature as well as their specific amino acid composition, we demonstrate that artificial suckerin-19 (S-19) can be engineered into nanocarriers for efficient drug delivery and gene transfection in vitro and in vivo. First, we demonstrate that S-19 self-assembles into β-sheet stabilized nanoparticles with controlled particle sizes of 100–200 nm that are able to encapsulate hydrophobic drugs for pH-dependent release in vitro, and that can effectively inhibit tumor growth in vivo. We also show that S-19 can complex and stabilize plasmid DNA, with the complexes stabilized by hydrophobic interactions of the β-sheet domains as opposed to electrostatic interactions commonly achieved with cationic polymers, thus lowering cytotoxicity. The elevated Histidine content of S-19 appears critical to trigger endosomal escape by the proton sponge effect, thereby ensuring efficient gene transfection both in vitro and in vivo. Our study demonstrates that S-19 represents a promising functional protein nanocarrier that could be used for various drug and gene delivery applications.

更新日期：2017-04-27

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