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, 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.affiliation: Department of Materials Science and Engineering, Northwestern University, 2220 Campus Drive, Evanston, IL 60208, USA; Simpson Querrey Institute for BioNanotechnology, Northwestern University, 303 East Superior Street, Lurie Suite 11-131, Chicago, IL 60611, USA.
authors.forename: R Helen
authors.initials: RH
authors.lastname: Zha
authors.affiliation: Simpson Querrey Institute for BioNanotechnology, Northwestern University, 303 East Superior Street, Lurie Suite 11-131, Chicago, IL 60611, USA.
authors.forename: Shantanu
authors.initials: S
authors.lastname: Sur
authors.affiliation: Simpson Querrey Institute for BioNanotechnology, Northwestern University, 303 East Superior Street, Lurie Suite 11-131, Chicago, IL 60611, USA.
authors.forename: Job
authors.initials: J
authors.lastname: Boekhoven
authors.affiliation: Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, 320 East Superior Street, Searle Suite 8-150, Chicago, IL 60611, USA.
authors.forename: Heidi Y
authors.initials: HY
authors.lastname: Shi
authors.affiliation: Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, 320 East Superior Street, Searle Suite 8-150, Chicago, IL 60611, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Materials Science and Engineering, Northwestern University, 2220 Campus Drive, Evanston, IL 60208, USA; Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA; Simpson Querrey Institute for BioNanotechnology, Northwestern University, 303 East Superior Street, Lurie Suite 11-131, Chicago, IL 60611, USA; Department of Medicine, Northwestern University, 251 East Huron Street, Galter Suite 3-150, Chicago, IL 60611, USA. Electronic address: s-stupp@northwestern.edu.
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Stupp
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D002942:Circular Dichroism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018716:Molecular Mimicry; D049329:Nanostructures; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D017433:Protein Structure, Secondary; D015843:Serpins / Q000737:chemistry*
chemical_list: D020533:Angiogenesis Inhibitors; D010455:Peptides; C085344:SERPIN-B5; D015843:Serpins
keywords: Anti-angiogenic; Maspin; Peptide amphiphile; Self-assembly; g-Helix