Enzymatic activation of cell-penetrating peptides in self-assembled nanostructures triggers fibre-to-micelle morphological transition

Yejiao Shi; Yang Hu; Guy Ochbaum; Ran Lin; Ronit Bitton; Honggang Cui; Helena S Azevedo

doi:10.1039/c7cc03512h

Enzymatic activation of cell-penetrating peptides in self-assembled nanostructures triggers fibre-to-micelle morphological transition

Chem Commun (Camb). 2017 Jul 4;53(52):7037-7040. doi: 10.1039/c7cc03512h. Epub 2017 Jun 14.

Authors

Yejiao Shi¹, Yang Hu², Guy Ochbaum³, Ran Lin², Ronit Bitton³, Honggang Cui², Helena S Azevedo¹

Affiliations

¹ School of Engineering and Materials Science, Institute of Bioengineering, Queen Mary, University of London, London, E1 4NS, UK. h.azevedo@qmul.ac.uk.
² Department of Chemical and Biomolecular Engineering and Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
³ Department of Chemical Engineering and the Ilza Katz, Institute for Nanoscale Science & Technology, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.

PMID: 28613294
DOI: 10.1039/c7cc03512h

Abstract

We report here a proof-of-concept design of a multi-domain cell-penetrating peptide amphiphile (CPPA) which can self-assemble into fibrous nanostructures and transform into spherical micelles upon enzymatic degradation by matrix metalloproteinase-2 (MMP-2) up-regulated in the tumour environment. Concomitant with this morphological transition, the cell-penetrating peptide (CPP), which was previously buried inside the CPPA fibers, could be presented on the surface of the CPPA micelles, enhancing their cell-penetrating ability. These multifunctional and enzyme-responsive CPP nanostructures hold potential as nanocarriers for tumour-targeted intracellular delivery of therapeutic and diagnostic agents.

MeSH terms

Cell-Penetrating Peptides / chemical synthesis
Cell-Penetrating Peptides / chemistry
Cell-Penetrating Peptides / metabolism*
Humans
Matrix Metalloproteinase 2 / metabolism*
Micelles*
Nanostructures / chemistry*
Surface-Active Agents / chemical synthesis
Surface-Active Agents / chemistry
Surface-Active Agents / metabolism*

Substances

Cell-Penetrating Peptides
Micelles
Surface-Active Agents
Matrix Metalloproteinase 2