skip to main content

DOE PAGESDOE PAGES

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

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:
Grant/Contract Number:
AC02-06CH11357; NCI CA060553; 5U54CA151880-03; CA079736
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.
Research Org:
Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
Sponsoring Org:
USDOE Office of Science (SC); National Institutes of Health (NIH); National Cancer Institute (NCI)
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES peptide amphiphile; self-assembly; maspin; g-Helix; anti-angiogenic
OSTI Identifier:
1168848
Alternate Identifier(s):
OSTI ID: 1168848