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Title: Supramolecular assembly of multifunctional maspin-mimetic nanostructures as a potent peptide-based angiogenesis inhibitor

Abstract

Aberrant angiogenesis plays a large role in pathologies ranging from tumor growth to macular degeneration. Anti-angiogenic proteins have thus come under scrutiny as versatile, potent therapeutics but face problems with purification and tissue retention. We report here on the synthesis of supramolecular nanostructures that mimic the anti-angiogenic activity of maspin, a class II tumor suppressor protein. These maspin-mimetic nanostructures are formed via self-assembly of small peptide amphiphiles containing the g-helix motif of maspin. Using tubulogenesis assays with human umbilical vein endothelial cells, we demonstrate that maspin-mimetic nanostructures show anti-angiogenic activity at concentrations that are significantly lower than those necessary for the g-helix peptide. Furthermore, in vivo assays in the chick chorioallantoic membrane show maspin-mimetic nanostructures to be effective over controls at inhibiting angiogenesis. Thus, in conclusion, the nanostructures investigated here offer an attractive alternative to the use of anti-angiogenic recombinant proteins in the treatment of cancer or other diseases involving abnormal blood vessel formation.

Authors:
 [1];  [2];  [2];  [3];  [3];  [4]
  1. Northwestern Univ., Evanston, IL (United States). Dept. of Materials Science and Engineering; Northwestern Univ., Evanston, IL (United States). Simpson Querrey Inst. for BioNanotechnology
  2. Northwestern Univ., Evanston, IL (United States). Simpson Querrey Inst. for BioNanotechnology
  3. Northwestern Univ., Evanston, IL (United States). Dept. of Molecular Pharmacology and Biological Chemistry
  4. Northwestern Univ., Evanston, IL (United States). Dept. of Materials Science and Engineering; Northwestern Univ., Evanston, IL (United States). Dept. of Chemistry; Northwestern Univ., Evanston, IL (United States). Simpson Querrey Inst. for BioNanotechnology; Northwestern Univ., Evanston, IL (United States). Dept. of Medicine
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE Office of Science (SC); National Institutes of Health (NIH); National Cancer Institute (NCI)
OSTI Identifier:
1168848
Alternate Identifier(s):
OSTI ID: 1251696
Grant/Contract Number:  
AC02-06CH11357; NCI CA060553; 5U54CA151880-03; CA079736
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Acta Biomaterialia
Additional Journal Information:
Journal Volume: 12; Journal Issue: C; Journal ID: ISSN 1742-7061
Publisher:
Acta Materialia, Inc.
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; peptide amphiphile; self-assembly; maspin; g-Helix; anti-angiogenic

Citation Formats

Zha, R. Helen, Sur, Shantanu, Boekhoven, Job, Shi, Heidi Y., Zhang, Ming, and Stupp, Samuel I. Supramolecular assembly of multifunctional maspin-mimetic nanostructures as a potent peptide-based angiogenesis inhibitor. United States: N. p., 2014. Web. doi:10.1016/j.actbio.2014.11.001.
Zha, R. Helen, Sur, Shantanu, Boekhoven, Job, Shi, Heidi Y., Zhang, Ming, & Stupp, Samuel I. Supramolecular assembly of multifunctional maspin-mimetic nanostructures as a potent peptide-based angiogenesis inhibitor. United States. https://doi.org/10.1016/j.actbio.2014.11.001
Zha, R. Helen, Sur, Shantanu, Boekhoven, Job, Shi, Heidi Y., Zhang, Ming, and Stupp, Samuel I. 2014. "Supramolecular assembly of multifunctional maspin-mimetic nanostructures as a potent peptide-based angiogenesis inhibitor". United States. https://doi.org/10.1016/j.actbio.2014.11.001. https://www.osti.gov/servlets/purl/1168848.
@article{osti_1168848,
title = {Supramolecular assembly of multifunctional maspin-mimetic nanostructures as a potent peptide-based angiogenesis inhibitor},
author = {Zha, R. Helen and Sur, Shantanu and Boekhoven, Job and Shi, Heidi Y. and Zhang, Ming and Stupp, Samuel I.},
abstractNote = {Aberrant angiogenesis plays a large role in pathologies ranging from tumor growth to macular degeneration. Anti-angiogenic proteins have thus come under scrutiny as versatile, potent therapeutics but face problems with purification and tissue retention. We report here on the synthesis of supramolecular nanostructures that mimic the anti-angiogenic activity of maspin, a class II tumor suppressor protein. These maspin-mimetic nanostructures are formed via self-assembly of small peptide amphiphiles containing the g-helix motif of maspin. Using tubulogenesis assays with human umbilical vein endothelial cells, we demonstrate that maspin-mimetic nanostructures show anti-angiogenic activity at concentrations that are significantly lower than those necessary for the g-helix peptide. Furthermore, in vivo assays in the chick chorioallantoic membrane show maspin-mimetic nanostructures to be effective over controls at inhibiting angiogenesis. Thus, in conclusion, the nanostructures investigated here offer an attractive alternative to the use of anti-angiogenic recombinant proteins in the treatment of cancer or other diseases involving abnormal blood vessel formation.},
doi = {10.1016/j.actbio.2014.11.001},
url = {https://www.osti.gov/biblio/1168848}, journal = {Acta Biomaterialia},
issn = {1742-7061},
number = C,
volume = 12,
place = {United States},
year = {Sat Nov 08 00:00:00 EST 2014},
month = {Sat Nov 08 00:00:00 EST 2014}
}

Journal Article:

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Cited by: 21 works
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Aqueous self-assembly of short hydrophobic peptides containing norbornene amino acid into supramolecular structures with spherical shape
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Drug delivery by supramolecular design
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Supramolecular Nanofibers Enhance Growth Factor Signaling by Increasing Lipid Raft Mobility
journal, April 2016