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Issue 49, 2020
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Modular design and self-assembly of multidomain peptides towards cytocompatible supramolecular cell penetrating nanofibers

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Abstract

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 of de novo designed multidomain peptides (MDPs) with a general sequence of Kx(QW)6Ey 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 vitro cell 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.

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

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Supplementary files

Article information


Submitted
29 May 2020
Accepted
29 Jul 2020
First published
10 Aug 2020

This article is Open Access

RSC Adv., 2020,10, 29469-29474
Article type
Paper

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

S. Yang and H. Dong, RSC Adv., 2020, 10, 29469
DOI: 10.1039/D0RA04748A

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

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    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
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    [Original citation] - Published by the PCCP Owner Societies.
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    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
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    [Original citation] - Published by The Royal Society of Chemistry.

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