DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

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:
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. Sat . "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},
journal = {Acta Biomaterialia},
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:

Citation Metrics:
Cited by: 21 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

The Hallmarks of Cancer
journal, January 2000


Angiogenesis in cancer and other diseases
journal, September 2000

  • Carmeliet, Peter; Jain, Rakesh K.
  • Nature, Vol. 407, Issue 6801
  • DOI: 10.1038/35025220

Angiogenesis and Cancer Prevention: A Vision
book, January 2007


Clinical translation of angiogenesis inhibitors
journal, October 2002

  • Kerbel, Robert; Folkman, Judah
  • Nature Reviews Cancer, Vol. 2, Issue 10
  • DOI: 10.1038/nrc905

Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells
journal, January 1994


Biological functions of maspin
journal, January 2006

  • Bailey, Caleb M.; Khalkhali-Ellis, Zhila; Seftor, Elisabeth A.
  • Journal of Cellular Physiology, Vol. 209, Issue 3
  • DOI: 10.1002/jcp.20782

Maspin is an angiogenesis inhibitor
journal, February 2000

  • Zhang, Ming; Volpert, Olga; Shi, Yihui H.
  • Nature Medicine, Vol. 6, Issue 2
  • DOI: 10.1038/72303

Maspin Regulates Endothelial Cell Adhesion and Migration through an Integrin Signaling Pathway
journal, October 2010


Maspin, the Molecular Bridge between the Plasminogen Activator System and β1 Integrin That Facilitates Cell Adhesion
journal, July 2011

  • Endsley, Michael P.; Hu, Yanqiu; Deng, Yong
  • Journal of Biological Chemistry, Vol. 286, Issue 28
  • DOI: 10.1074/jbc.M111.235788

G-helix of Maspin Mediates Effects on Cell Migration and Adhesion
journal, November 2010

  • Ravenhill, Lorna; Wagstaff, Laura; Edwards, Dylan R.
  • Journal of Biological Chemistry, Vol. 285, Issue 47
  • DOI: 10.1074/jbc.M110.177253

The High Resolution Crystal Structure of the Human Tumor Suppressor Maspin Reveals a Novel Conformational Switch in the G-helix
journal, June 2005

  • Law, Ruby H. P.; Irving, James A.; Buckle, Ashley M.
  • Journal of Biological Chemistry, Vol. 280, Issue 23
  • DOI: 10.1074/jbc.M412043200

Self-Assembly and Mineralization of Peptide-Amphiphile Nanofibers
journal, November 2001

  • Hartgerink, Jeffrey D.; Beniash, Elia; Stupp, Samuel I.
  • Science, Vol. 294, Issue 5547, p. 1684-1688
  • DOI: 10.1126/science.1063187

Peptide-amphiphile nanofibers: A versatile scaffold for the preparation of self-assembling materials
journal, April 2002

  • Hartgerink, J. D.; Beniash, E.; Stupp, S. I.
  • Proceedings of the National Academy of Sciences, Vol. 99, Issue 8, p. 5133-5138
  • DOI: 10.1073/pnas.072699999

Self-assembly of peptide amphiphiles: From molecules to nanostructures to biomaterials
journal, January 2010

  • Cui, Honggang; Webber, Matthew J.; Stupp, Samuel I.
  • Biopolymers, Vol. 94, Issue 1, p. 1-18
  • DOI: 10.1002/bip.21328

Emerging peptide nanomedicine to regenerate tissues and organs: Symposium: Peptide nanomedicine
journal, January 2010


Peptide self-assembly for crafting functional biological materials
journal, December 2011

  • Matson, John B.; Zha, R. Helen; Stupp, Samuel I.
  • Current Opinion in Solid State and Materials Science, Vol. 15, Issue 6
  • DOI: 10.1016/j.cossms.2011.08.001

Supramolecular Nanofibers of Peptide Amphiphiles for Medicine
journal, August 2013

  • Webber, Matthew J.; Berns, Eric J.; Stupp, Samuel I.
  • Israel Journal of Chemistry, Vol. 53, Issue 8
  • DOI: 10.1002/ijch.201300046

The internal structure of self-assembled peptide amphiphiles nanofibers
journal, January 2007

  • Jiang, Hongzhou; Guler, Mustafa O.; Stupp, Samuel I.
  • Soft Matter, Vol. 3, Issue 4
  • DOI: 10.1039/b614426h

Molecular Simulation Study of Peptide Amphiphile Self-Assembly
journal, February 2008

  • Velichko, Yuri S.; Stupp, Samuel I.; de la Cruz, Monica Olvera
  • The Journal of Physical Chemistry B, Vol. 112, Issue 8
  • DOI: 10.1021/jp074420n

Supramolecular crafting of cell adhesion
journal, November 2007


Supramolecular nanostructures that mimic VEGF as a strategy for ischemic tissue repair
journal, August 2011

  • Webber, M. J.; Tongers, J.; Newcomb, C. J.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 33
  • DOI: 10.1073/pnas.1016546108

Dynamic in vivo biocompatibility of angiogenic peptide amphiphile nanofibers
journal, October 2009


Shape effects of filaments versus spherical particles in flow and drug delivery
journal, March 2007

  • Geng, Yan; Dalhaimer, Paul; Cai, Shenshen
  • Nature Nanotechnology, Vol. 2, Issue 4
  • DOI: 10.1038/nnano.2007.70

Self-assembling glucagon-like peptide 1-mimetic peptide amphiphiles for enhanced activity and proliferation of insulin-secreting cells
journal, May 2012


Protein secondary structure analyses from circular dichroism spectroscopy: Methods and reference databases
journal, May 2008

  • Whitmore, Lee; Wallace, B. A.
  • Biopolymers, Vol. 89, Issue 5, p. 392-400
  • DOI: 10.1002/bip.20853

Structure-based conformational preferences of amino acids
journal, October 1999

  • Koehl, P.; Levitt, M.
  • Proceedings of the National Academy of Sciences, Vol. 96, Issue 22
  • DOI: 10.1073/pnas.96.22.12524

Self-Assembly of Peptide−Amphiphile Nanofibers:  The Roles of Hydrogen Bonding and Amphiphilic Packing
journal, June 2006

  • Paramonov, Sergey E.; Jun, Ho-Wook; Hartgerink, Jeffrey D.
  • Journal of the American Chemical Society, Vol. 128, Issue 22
  • DOI: 10.1021/ja060573x

Critical micelle concentration of surfactants in aqueous buffered and unbuffered systems
journal, August 2005

  • Fuguet, Elisabet; Ràfols, Clara; Rosés, Martí
  • Analytica Chimica Acta, Vol. 548, Issue 1-2
  • DOI: 10.1016/j.aca.2005.05.069

Engineered and designed peptide-based fibrous biomaterials
journal, March 2004

  • MacPhee, Cait E.; Woolfson, Derek N.
  • Current Opinion in Solid State and Materials Science, Vol. 8, Issue 2
  • DOI: 10.1016/j.cossms.2004.01.010

Induction of protein-like molecular architecture by monoalkyl hydrocarbon chains
journal, January 2000


The design, synthesis, and crystallization of an alpha-helical peptide
journal, January 1986

  • Eisenberg, David; Wilcox, William; Eshita, Steven M.
  • Proteins: Structure, Function, and Genetics, Vol. 1, Issue 1
  • DOI: 10.1002/prot.340010105

Design of a 4-helix bundle protein: synthesis of peptides which self-associate into a helical protein
journal, October 1987

  • Ho, Siew Peng; DeGrado, William F.
  • Journal of the American Chemical Society, Vol. 109, Issue 22, p. 6751-6758
  • DOI: 10.1021/ja00256a032

Maspin is physically associated with β1 integrin regulating cell adhesion in mammary epithelial cells
journal, May 2006

  • Cella, Nathalie; Contreras, Alejandro; Latha, Khatri
  • The FASEB Journal, Vol. 20, Issue 9
  • DOI: 10.1096/fj.05-5500fje

Binding of Extracellular Maspin to β1 Integrins Inhibits Vascular Smooth Muscle Cell Migration
journal, October 2009

  • Bass, Rosemary; Wagstaff, Laura; Ravenhill, Lorna
  • Journal of Biological Chemistry, Vol. 284, Issue 40
  • DOI: 10.1074/jbc.M109.038919

In vitro angiogenesis: endothelial cell tube formation on gelled basement membrane extract
journal, March 2010


Angiostatin: A Circulating Endothelial Cell Inhibitor That Suppresses Angiogenesis and Tumor Growth
journal, January 1994

  • O'Reilly, M. S.; Holmgren, L.; Shing, Y.
  • Cold Spring Harbor Symposia on Quantitative Biology, Vol. 59, Issue 0
  • DOI: 10.1101/SQB.1994.059.01.052

Captopril inhibits angiogenesis and slows the growth of experimental tumors in rats.
journal, August 1996

  • Volpert, O. V.; Ward, W. F.; Lingen, M. W.
  • Journal of Clinical Investigation, Vol. 98, Issue 3
  • DOI: 10.1172/JCI118838

Works referencing / citing this record:

Aqueous self-assembly of short hydrophobic peptides containing norbornene amino acid into supramolecular structures with spherical shape
journal, January 2016

  • Ruffoni, Alessandro; Cavanna, Maria V.; Argentiere, Simona
  • RSC Advances, Vol. 6, Issue 93
  • DOI: 10.1039/c6ra17116h

Drug delivery by supramolecular design
journal, January 2017

  • Webber, Matthew J.; Langer, Robert
  • Chemical Society Reviews, Vol. 46, Issue 21
  • DOI: 10.1039/c7cs00391a

Supramolecular Nanofibers Enhance Growth Factor Signaling by Increasing Lipid Raft Mobility
journal, April 2016