Switching of macromolecular ligand display by thermoresponsive polymers mediates endocytosis of multi-conjugate nanoparticles

Sayers, Edward and Magnusson, Johannes Pall and Moody, Paul and Mastrotto, Francesca and Conte, Claudia and Brazzale, Chiara and Borri, Paola and Caliceti, Paolo and Watson, Peter and Mantovani, Giuseppe and Aylott, Jonathan W. and Salmaso, Stefano and Jones, Arwyn T. and Alexander, Cameron (2018) Switching of macromolecular ligand display by thermoresponsive polymers mediates endocytosis of multi-conjugate nanoparticles. Bioconjugate Chemistry . ISSN 1520-4812

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Abstract

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.

Item Type: Article
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
Schools/Departments: University of Nottingham, UK > Faculty of Science > School of Pharmacy
Identification Number: https://doi.org/10.1021/acs.bioconjchem.7b00704
Depositing User: Eprints, Support
Date Deposited: 27 Feb 2018 11:12
Last Modified: 11 Jun 2018 00:28
URI: http://eprints.nottingham.ac.uk/id/eprint/50046

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