Edward Sayers
Switching of Macromolecular Ligand Display by Thermoresponsive Polymers Mediates Endocytosis of Multiconjugate Nanoparticles
Sayers, Edward; Magnusson, Johannes Pall; Moody, Paul; Mastrotto, Francesca; Conte, Claudia; Brazzale, Chiara; Borri, Paola; Caliceti, Paolo; Watson, Peter; Mantovani, Giuseppe; Aylott, Jonathan; Salmaso, Stefano; Jones, Arwyn T.; Alexander, Cameron
Authors
Johannes Pall Magnusson
Paul Moody
Francesca Mastrotto
Claudia Conte
Chiara Brazzale
Paola Borri
Paolo Caliceti
Peter Watson
GIUSEPPE MANTOVANI giuseppe.mantovani@nottingham.ac.uk
Associate Professor
JONATHAN AYLOTT JON.AYLOTT@NOTTINGHAM.AC.UK
Professor of Analytical Science
Stefano Salmaso
Arwyn T. Jones
Professor CAMERON ALEXANDER CAMERON.ALEXANDER@NOTTINGHAM.AC.UK
Professor of Polymer Therapeutics
Abstract
© 2018 American Chemical Society. Ligand-mediated targeting and internalization of plasma membrane receptors is central to cellular function. These types of receptors have accordingly been investigated as targets to facilitate entry of diagnostic and therapeutic constructs into cells. However, there remains a need to characterize how receptor targeting agents on nanoparticles interact at surface receptors and whether it is possible to control these interactions via exogenous stimuli. Here, we describe the switchable display of the iron-transporting protein, transferrin (Tf), at the surface of thermoresponsive polymer-coated gold nanoparticles and show that internalization of the coated nanoparticles into target cells changes across temperature ranges over which transferrin is expected to be sterically "hidden" by an extended polymer chain and then "revealed" by polymer chain collapse. The switching process is dependent on the numbers of transferrin molecules and thermoresponsive polymer chains attached and whether the assay temperature is above or below the transition temperatures of the responsive polymers at the nanoparticle surfaces. Significantly, however, the control of internalization is critically reliant on overall nanoparticle colloidal stability while the thermoresponsive component of the surface undergoes conformational change. The data show that the cell entry function of complex and large biomolecule ligands can be modulated by polymer-induced accessibility change but that a simple "hide and reveal" mechanism for ligand display following polymer chain collapse is insufficient to account for nanoparticle uptake and subsequent intracellular trafficking.
Citation
Sayers, E., Magnusson, J. P., Moody, P., Mastrotto, F., Conte, C., Brazzale, C., …Alexander, C. (2018). Switching of Macromolecular Ligand Display by Thermoresponsive Polymers Mediates Endocytosis of Multiconjugate Nanoparticles. Bioconjugate Chemistry, 29(4), 1030-1046. https://doi.org/10.1021/acs.bioconjchem.7b00704
Journal Article Type | Article |
---|---|
Acceptance Date | Feb 25, 2018 |
Online Publication Date | Feb 26, 2018 |
Publication Date | Apr 18, 2018 |
Deposit Date | Feb 27, 2018 |
Publicly Available Date | Mar 29, 2024 |
Journal | Bioconjugate Chemistry |
Print ISSN | 1043-1802 |
Electronic ISSN | 1520-4812 |
Publisher | American Chemical Society |
Peer Reviewed | Peer Reviewed |
Volume | 29 |
Issue | 4 |
Pages | 1030-1046 |
DOI | https://doi.org/10.1021/acs.bioconjchem.7b00704 |
Public URL | https://nottingham-repository.worktribe.com/output/916727 |
Publisher URL | https://pubs.acs.org/doi/10.1021/acs.bioconjchem.7b00704 |
Additional Information | This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in Bioconjugate Chemistry, copyright ©2018 American Chemical Society after peer review. To access the final edited and published work see [insert ACS Article on Request author-directed link to Published Work, see https://pubs.acs.org/doi/10.1021/acs.bioconjchem.7b00704 |
Files
Cell Scalextric main paper 2018 Revised FINAL.pdf
(1.2 Mb)
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Cell Scalextric Main Paper ESI resubmitted.pdf
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