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Avidity and Cell Uptake of Integrin-Targeting Polypeptide Micelles is Strongly Shape-Dependent.
- 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.
- Subjects :
- Animals
Drosophila Proteins genetics
Drosophila melanogaster chemistry
Drosophila melanogaster genetics
Elastin chemistry
Elastin genetics
Fibronectin Type III Domain genetics
Fibronectins genetics
Humans
Ligands
Micelles
Peptides chemistry
Peptides pharmacology
Temperature
Tropoelastin genetics
Drosophila Proteins chemistry
Drug Delivery Systems
Fibronectins chemistry
Nanoparticles chemistry
Tropoelastin chemistry
Subjects
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