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

Publication ,  Journal Article
Dzuricky, M; Xiong, S; Weber, P; Chilkoti, A
Published in: Nano letters
September 2019

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.

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Published In

Nano letters

DOI

EISSN

1530-6992

ISSN

1530-6984

Publication Date

September 2019

Volume

19

Issue

9

Start / End Page

6124 / 6132

Related Subject Headings

  • Tropoelastin
  • Temperature
  • Peptides
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Micelles
  • Ligands
  • Humans
  • Fibronectins
  • Fibronectin Type III Domain
 

Citation

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MLA
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Dzuricky, M., Xiong, S., Weber, P., & Chilkoti, A. (2019). Avidity and Cell Uptake of Integrin-Targeting Polypeptide Micelles is Strongly Shape-Dependent. Nano Letters, 19(9), 6124–6132. https://doi.org/10.1021/acs.nanolett.9b02095
Dzuricky, Michael, Sinan Xiong, Patrick Weber, and Ashutosh Chilkoti. “Avidity and Cell Uptake of Integrin-Targeting Polypeptide Micelles is Strongly Shape-Dependent.Nano Letters 19, no. 9 (September 2019): 6124–32. https://doi.org/10.1021/acs.nanolett.9b02095.
Dzuricky M, Xiong S, Weber P, Chilkoti A. Avidity and Cell Uptake of Integrin-Targeting Polypeptide Micelles is Strongly Shape-Dependent. Nano letters. 2019 Sep;19(9):6124–32.
Dzuricky, Michael, et al. “Avidity and Cell Uptake of Integrin-Targeting Polypeptide Micelles is Strongly Shape-Dependent.Nano Letters, vol. 19, no. 9, Sept. 2019, pp. 6124–32. Epmc, doi:10.1021/acs.nanolett.9b02095.
Dzuricky M, Xiong S, Weber P, Chilkoti A. Avidity and Cell Uptake of Integrin-Targeting Polypeptide Micelles is Strongly Shape-Dependent. Nano letters. 2019 Sep;19(9):6124–6132.
Journal cover image

Published In

Nano letters

DOI

EISSN

1530-6992

ISSN

1530-6984

Publication Date

September 2019

Volume

19

Issue

9

Start / End Page

6124 / 6132

Related Subject Headings

  • Tropoelastin
  • Temperature
  • Peptides
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Micelles
  • Ligands
  • Humans
  • Fibronectins
  • Fibronectin Type III Domain