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Concentration-Independent Multivalent Targeting of Cancer Cells by Genetically Encoded Core-Crosslinked Elastin/Resilin-like Polypeptide Micelles.

Publication ,  Journal Article
Weber, P; Dzuricky, M; Min, J; Jenkins, I; Chilkoti, A
Published in: Biomacromolecules
October 2021

Valency is a fundamental principle to control macromolecular interactions and is used to target specific cell types by multivalent ligand-receptor interactions using self-assembled nanoparticle carriers. At the concentrations encountered in solid tumors upon systemic administration, these nanoparticles are, however, likely to show critical micelle concentration (CMC)-dependent disassembly and thus loss of function. To overcome this limitation, core-crosslinkable micelles of genetically encoded resilin-/elastin-like diblock polypeptides were recombinantly synthesized. The amphiphilic constructs were covalently photo-crosslinked through the genetically encoded unnatural amino acid para-azidophenylalanine in their hydrophobic block and they carried different anticancer ligands on their hydrophilic block: the wild-type tenth human fibronectin type III domain, a GRGDSPAS peptide-both targeting αvβ3 integrin-and an engineered variant of the third fibronectin type III domain of tenascin C that is a death receptor 5 agonist. Although uncrosslinked micelles lost most of their targeting ability below their CMC, the crosslinked analogues remained active at concentrations up to 1000-fold lower than the CMC, with binding affinities that are comparable to antibodies.

Duke Scholars

Published In

Biomacromolecules

DOI

EISSN

1526-4602

ISSN

1525-7797

Publication Date

October 2021

Volume

22

Issue

10

Start / End Page

4347 / 4356

Related Subject Headings

  • Polymers
  • Peptides
  • Neoplasms
  • Micelles
  • Insect Proteins
  • Humans
  • Elastin
  • 40 Engineering
  • 34 Chemical sciences
  • 31 Biological sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Weber, P., Dzuricky, M., Min, J., Jenkins, I., & Chilkoti, A. (2021). Concentration-Independent Multivalent Targeting of Cancer Cells by Genetically Encoded Core-Crosslinked Elastin/Resilin-like Polypeptide Micelles. Biomacromolecules, 22(10), 4347–4356. https://doi.org/10.1021/acs.biomac.1c00897
Weber, Patrick, Michael Dzuricky, Junseon Min, Irene Jenkins, and Ashutosh Chilkoti. “Concentration-Independent Multivalent Targeting of Cancer Cells by Genetically Encoded Core-Crosslinked Elastin/Resilin-like Polypeptide Micelles.Biomacromolecules 22, no. 10 (October 2021): 4347–56. https://doi.org/10.1021/acs.biomac.1c00897.
Weber, Patrick, et al. “Concentration-Independent Multivalent Targeting of Cancer Cells by Genetically Encoded Core-Crosslinked Elastin/Resilin-like Polypeptide Micelles.Biomacromolecules, vol. 22, no. 10, Oct. 2021, pp. 4347–56. Epmc, doi:10.1021/acs.biomac.1c00897.
Weber P, Dzuricky M, Min J, Jenkins I, Chilkoti A. Concentration-Independent Multivalent Targeting of Cancer Cells by Genetically Encoded Core-Crosslinked Elastin/Resilin-like Polypeptide Micelles. Biomacromolecules. 2021 Oct;22(10):4347–4356.
Journal cover image

Published In

Biomacromolecules

DOI

EISSN

1526-4602

ISSN

1525-7797

Publication Date

October 2021

Volume

22

Issue

10

Start / End Page

4347 / 4356

Related Subject Headings

  • Polymers
  • Peptides
  • Neoplasms
  • Micelles
  • Insect Proteins
  • Humans
  • Elastin
  • 40 Engineering
  • 34 Chemical sciences
  • 31 Biological sciences