用于增强稳定性和免疫相容性的 DNA 纳米结构的蛋白质涂层,Advanced Healthcare Materials

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用于增强稳定性和免疫相容性的 DNA 纳米结构的蛋白质涂层
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2017-07-24 , DOI: 10.1002/adhm.201700692
Henni Auvinen ₁ , Hongbo Zhang _{2,

3} , Nonappa ₄ , Alisa Kopilow ₁ , Elina H Niemelä ₅ , Sami Nummelin ₁ , Alexandra Correia ₂ , Hélder A Santos _{2,

6} , Veikko Linko ₁ , Mauri A Kostiainen ₁

Affiliation

完全可寻址的 DNA 纳米结构，尤其是 DNA 折纸，具有作为固有生物相容性和多功能分子平台的巨大潜力。然而，它们在治疗中作为递送载体的用途因其稳定性低和转染率低而受到影响。这项研究表明，DNA 折纸可以被精确定义的一对一蛋白质-树突结合物包被，以解决上述问题。偶联物的树突部分作为阳离子结合域，通过静电相互作用连接到带负电荷的 DNA 折纸表面。该蛋白质通过半胱氨酸-马来酰亚胺键连接到树突上，使模块化方法高度通用。这项工作演示了使用两种不同蛋白质的涂层：牛血清白蛋白 (BSA) 和 II 类疏水蛋白 (HFBI)。结果表明，BSA 涂层显着提高了折纸对核酸内切酶 (DNase I) 的稳定性，并增强了对人胚胎肾 (HEK293) 细胞的转染。重要的是，观察到 BSA 涂层减弱了小鼠原代脾细胞中免疫反应的激活。血清白蛋白是血液中含量最丰富的蛋白质，具有较长的循环半衰期，已在临床上获得批准用于药物输送。因此，设想所提出的系统可以开辟更多的机会来调整生物环境中 DNA 纳米结构的特性，并使它们能够用于各种递送应用。据观察，BSA 涂层减弱了小鼠原代脾细胞免疫反应的激活。血清白蛋白是血液中含量最丰富的蛋白质，具有较长的循环半衰期，已在临床上获得批准用于药物输送。因此，设想所提出的系统可以开辟更多的机会来调整生物环境中 DNA 纳米结构的特性，并使它们能够用于各种递送应用。据观察，BSA 涂层减弱了小鼠原代脾细胞免疫反应的激活。血清白蛋白是血液中含量最丰富的蛋白质，具有较长的循环半衰期，已在临床上获得批准用于药物输送。因此，设想所提出的系统可以开辟更多的机会来调整生物环境中 DNA 纳米结构的特性，并使它们能够用于各种递送应用。

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Protein Coating of DNA Nanostructures for Enhanced Stability and Immunocompatibility

Fully addressable DNA nanostructures, especially DNA origami, possess huge potential to serve as inherently biocompatible and versatile molecular platforms. However, their use as delivery vehicles in therapeutics is compromised by their low stability and poor transfection rates. This study shows that DNA origami can be coated by precisely defined one‐to‐one protein‐dendron conjugates to tackle the aforementioned issues. The dendron part of the conjugate serves as a cationic binding domain that attaches to the negatively charged DNA origami surface via electrostatic interactions. The protein is attached to dendron through cysteine‐maleimide bond, making the modular approach highly versatile. This work demonstrates the coating using two different proteins: bovine serum albumin (BSA) and class II hydrophobin (HFBI). The results reveal that BSA‐coating significantly improves the origami stability against endonucleases (DNase I) and enhances the transfection into human embryonic kidney (HEK293) cells. Importantly, it is observed that BSA‐coating attenuates the activation of immune response in mouse primary splenocytes. Serum albumin is the most abundant protein in the blood with a long circulation half‐life and has already found clinically approved applications in drug delivery. It is therefore envisioned that the proposed system can open up further opportunities to tune the properties of DNA nanostructures in biological environment, and enable their use in various delivery applications.

更新日期：2017-07-24

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