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

Published

Journal Article

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 αvβ3 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.

Full Text

Duke Authors

Cited Authors

  • Dzuricky, M; Xiong, S; Weber, P; Chilkoti, A

Published Date

  • September 2019

Published In

Volume / Issue

  • 19 / 9

Start / End Page

  • 6124 - 6132

PubMed ID

  • 31389705

Pubmed Central ID

  • 31389705

Electronic International Standard Serial Number (EISSN)

  • 1530-6992

International Standard Serial Number (ISSN)

  • 1530-6984

Digital Object Identifier (DOI)

  • 10.1021/acs.nanolett.9b02095

Language

  • eng