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Avidity and Cell Uptake of Integrin-Targeting Polypeptide Micelles is Strongly Shape-Dependent.

Authors :
Dzuricky M
Xiong S
Weber P
Chilkoti A
Source :
Nano letters [Nano Lett] 2019 Sep 11; Vol. 19 (9), pp. 6124-6132. Date of Electronic Publication: 2019 Aug 12.
Publication Year :
2019

Abstract

We describe a genetically encoded micelle for targeted delivery consisting of a diblock polypeptide with segments derived from repetitive protein motifs inspired by Drosophila melanogaster Rec-1 resilin and human tropoelastin with a C-terminal fusion of an integrin-targeting fibronectin type III domain. By systematically varying the weight fraction of the hydrophilic elastin-like polypeptide (ELP) block and molecular weight of the diblock polypeptide, we designed micelles of different morphologies that modulate the binding avidity of the human wild-type 10th fibronectin domain (Fn3) as a function of shape. We show that wormlike micelles that present the Fn3 domain have a 1000-fold greater avidity for the α <subscript>v</subscript> β <subscript>3</subscript> receptor compared to the monomer ligand and an avidity that is greater than a clinically relevant antibody that is driven by their multivalency. The amplified avidity of these micelles leads to significantly increased cellular internalization, a feature that may have utility for the intracellular delivery of drugs that are loaded into the core of these micelles.

Details

Language :
English
ISSN :
1530-6992
Volume :
19
Issue :
9
Database :
MEDLINE
Journal :
Nano letters
Publication Type :
Academic Journal
Accession number :
31389705
Full Text :
https://doi.org/10.1021/acs.nanolett.9b02095