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通过体外拆分手性构建模块并重新组装来构建多功能蛋白纳米颗粒。

Engineering multifunctional protein nanoparticles by in vitro disassembling and reassembling of heterologous building blocks.

机构信息

Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de la Santa Creu i Sant Pau, E-08025 Barcelona, Spain. CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.

出版信息

Nanotechnology. 2017 Dec 15;28(50):505102. doi: 10.1088/1361-6528/aa963e.

DOI:10.1088/1361-6528/aa963e
PMID:29072576
Abstract

The engineering of protein self-assembling at the nanoscale allows the generation of functional and biocompatible materials, which can be produced by easy biological fabrication. The combination of cationic and histidine-rich stretches in fusion proteins promotes oligomerization as stable protein-only regular nanoparticles that are composed by a moderate number of building blocks. Among other applications, these materials are highly appealing as tools in targeted drug delivery once empowered with peptidic ligands of cell surface receptors. In this context, we have dissected here this simple technological platform regarding the controlled disassembling and reassembling of the composing building blocks. By applying high salt and imidazole in combination, nanoparticles are disassembled in a process that is fully reversible upon removal of the disrupting agents. By taking this approach, we accomplish here the in vitro generation of hybrid nanoparticles formed by heterologous building blocks. This fact demonstrates the capability to generate multifunctional and/or multiparatopic or multispecific materials usable in nanomedical applications.

摘要

蛋白质自组装的纳米工程允许功能性和生物相容性材料的产生,这些材料可以通过简单的生物制造生产。融合蛋白中阳离子和富含组氨酸的伸展部分的组合促进了作为稳定的仅由蛋白质组成的规则纳米颗粒的寡聚化,这些颗粒由适度数量的构建块组成。在其他应用中,这些材料作为靶向药物输送的工具非常有吸引力,一旦赋予细胞表面受体的肽配体。在这种情况下,我们在这里对组成构建块的受控拆卸和重新组装进行了剖析。通过应用高盐和咪唑的组合,纳米颗粒在完全可逆的过程中被拆卸,一旦去除了破坏剂。通过采用这种方法,我们在这里实现了由异源构建块形成的杂化纳米颗粒的体外生成。这一事实证明了能够生成可用于纳米医学应用的多功能和/或多价或多特异性材料的能力。

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