Bimodal brush-functionalized nanoparticles selective to receptor surface density.
File(s)pnas.2208377120.pdf (764.89 KB)
Published version
Author(s)
Phan, Huu Trong
Lauzon, Dominic
Vallée-Bélisle, Alexis
Angioletti-Uberti, Stefano
Leblond Chain, Jeanne
Type
Journal Article
Abstract
Nanoparticles or drug carriers which can selectively bind to cells expressing receptors above a certain threshold surface density are very promising for targeting cells overexpressing specific receptors under pathological conditions. Simulations and theoretical studies have suggested that such selectivity can be enhanced by functionalizing nanoparticles with a bimodal polymer monolayer (BM) containing shorter ligated chains and longer inert protective chains. However, a systematic study of the effect of these parameters under tightly controlled conditions is still missing. Here, we develop well-defined and highly specific platforms mimicking particle-cell interface using surface chemistry to provide a experimental proof of such selectivity. Using surface plasmon resonance and atomic force microscopy, we report the selective adsorption of BM-functionalized nanoparticles, and especially, a significant enhanced selective behavior by using a BM with longer protective chains. Furthermore, a model is also developed to describe the repulsive contribution of the protective brush to nanoparticle adsorption. This model is combined with super-selectivity theory to support experimental findings and shows that the observed selectivity is due to the steric energy barrier which requires a high number of ligand-receptor bonds to allow nanoparticle adsorption. Finally, the results show how the relative length and molar ratio of two chains can be tuned to target a threshold surface density of receptors and thus lay the foundation for the rational design of BM-functionalized nanoparticles for selective targeting.
Date Issued
2023-01-17
Date Acceptance
2022-11-25
Citation
Proceedings of the National Academy of Sciences of USA, 2023, 120 (3), pp.1-7
ISSN
0027-8424
Publisher
National Academy of Sciences
Start Page
1
End Page
7
Journal / Book Title
Proceedings of the National Academy of Sciences of USA
Volume
120
Issue
3
Copyright Statement
Copyright © 2023 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/36630450
Subjects
bimodal brush
functionalization
nanoparticle
receptor surface density
selectivity
Nanoparticles
Polymers
Ligands
Models, Theoretical
Surface Plasmon Resonance
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2023-01-11