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Modular design and self-assembly of multidomain peptides towards cytocompatible supramolecular cell penetrating nanofibers

机译:多麦草肽对细胞相容的超分子细胞穿透纳米纤维的模块化设计和自组装

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摘要

The discovery of cell penetrating peptides (CPPs) with unique membrane activity has inspired the design and synthesis of a variety of cell penetrating macromolecules, which offer tremendous opportunity and promise for intracellular delivery of a variety of imaging probes and therapeutics. While cell penetrating macromolecules can be designed and synthesized to have equivalent or even superior cell penetrating activity compared with natural CPPs, most of them suffer from moderate to severe cytotoxicity. Inspired by recent advances in peptide self-assembly and cell penetrating macromolecules, in this work, we demonstrated a new class of peptide assemblies with intrinsic cell penetrating activity and excellent cytocompatibility. Supramolecular assemblies were formed through the self-assembly ofde novodesigned multidomain peptides (MDPs) with a general sequence of K-x(QW)(6)E(y)in which the numbers of lysine and glutamic acid can be varied to control supramolecular assembly, morphology and cell penetrating activity. Both supramolecular spherical particles and nanofibers exhibit much higher cell penetrating activity than monomeric MDPs while supramolecular nanofibers were found to further enhance the cell penetrating activity of MDPs.In vitrocell uptake results suggested that the supramolecular cell penetrating nanofibers undergo macropinocytosis-mediated internalization and they are capable of escaping from the lysosome to reach the cytoplasm, which highlights their great potential as highly effective intracellular therapeutic delivery vehicles and imaging probes.
机译:具有独特膜活性的细胞穿透肽(CPP)的发现启发了各种细胞穿透大分子的设计和合成,为细胞内递送了各种成像探针和治疗剂提供了巨大的机遇和承诺。虽然细胞穿透大分子可以设计和合成,但与天然CPP相比具有等同的或甚至优异的细胞穿透活性,其中大多数受到中度至严重的细胞毒性。在这项工作中,肽自组装和细胞渗透大分子的最近进展的启发,我们证明了一种具有内在细胞穿透活性的新类肽组件和优异的细胞组合。通过NododeSige多域肽(MDP)的自组装形成超分子组件,其中kx(qw)(6)e(y)的一般序列,其中赖氨酸和谷氨酸的数量可以变化以控制超分子组装,形态和细胞穿透活动。超分子球形颗粒和纳米纤维均表现出比单体MDP更高的细胞穿透活性,同时发现超分子纳米纤维进一步增强了MDPS的细胞穿透活性。在vitrocell吸收结果表明,超分子细胞穿透纳米纤维经过大滴虫症介导的内化,它们有能力逃离溶酶体以达到细胞质,这突出了它们作为高效细胞内治疗递送车辆和成像探针的巨大潜力。

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  • 来源
    《RSC Advances》 |2020年第49期|共6页
  • 作者

    Yang Su; Dong He;

  • 作者单位

    Univ Texas Arlington Dept Chem &

    Biochem Arlington TX 76019 USA;

    Univ Texas Arlington Dept Chem &

    Biochem Arlington TX 76019 USA;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
  • 关键词

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