Ellacott, Sean H., Sanchez-Cano, Carlos, Mansfield, Edward D. H., Rho, Julia Y., Song, Ji-Inn, Peltier, Raoul and Perrier, Sébastien (2021) Comparative study of the cellular uptake and intracellular behavior of a library of cyclic peptide–polymer nanotubes with different self-assembling properties. Biomacromolecules, 22 (2). pp. 710-722. doi:10.1021/acs.biomac.0c01512

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Abstract

Particle shape has been described as a key factor in improving cell internalization and biodistribution among the different properties investigated for drug-delivery systems. In particular, tubular structures have been identified as promising candidates for improving drug delivery. Here, we investigate the influence of different design elements of cyclic peptide–polymer nanotubes (CPNTs) on cellular uptake including the nature and length of the polymer and the cyclic peptide building block. By varying the composition of these cyclic peptide–polymer conjugates, a library of CPNTs of lengths varying from a few to over a 150 nm were synthesized and characterized using scattering techniques (small-angle neutron scattering and static light scattering). In vitro studies with fluorescently labeled CPNTs have shown that nanotubes comprised of a single polymer arm with a size between 8 and 16 nm were the most efficiently taken up by three different mammalian cell lines. A mechanistic study on multicellular tumor spheroids has confirmed the ability of these compounds to penetrate to their core. Variations in the proportion of paracellular and transcellular uptake with the self-assembling potential of the CPNT were also observed, giving key insights about the behavior of CPNTs in cellular systems.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry Q Science > QP Physiology R Medicine > RS Pharmacy and materia medica
Divisions:	Faculty of Science > Chemistry
Library of Congress Subject Headings (LCSH):	Cyclic peptides , Nanotubes, Self-assembly (Chemistry), Drug delivery systems, Cellular signal transduction
Journal or Publication Title:	Biomacromolecules
Publisher:	American Chemical Society
ISSN:	1525-7797
Official Date:	8 February 2021
Dates:	Date Event 8 February 2021 Published 22 December 2020 Available 22 December 2020 Accepted
Volume:	22
Number:	2
Page Range:	pp. 710-722
DOI:	10.1021/acs.biomac.0c01512
Status:	Peer Reviewed
Publication Status:	Published
Publisher Statement:	This document is the Accepted Manuscript version of a Published Work that appeared in final form in Biomacromolecules, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.biomac.0c01512
Access rights to Published version:	Restricted or Subscription Access
RIOXX Funder/Project Grant:	Project/Grant ID RIOXX Funder Name Funder ID TUSUPO 647106 European Research Council http://dx.doi.org/10.13039/501100000781 C53561/A19933 Cancer Research UK http://dx.doi.org/10.13039/501100000289 C53561/A19933 [EPSRC] Engineering and Physical Sciences Research Council http://dx.doi.org/10.13039/501100000266 RB1720086 [STFC] Science and Technology Facilities Council http://dx.doi.org/10.13039/501100000271

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