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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1-10 |
| Number of pages | 10 |
| Journal | Acta Biomaterialia |
| Volume | 12 |
| Issue number | C |
| DOIs | |
| State | Published - 2015 |
Funding
This work was supported by a grant from NIH/NCI # 5U54CA151880-03 . M.Z. was additionally supported by NCI # CA079736 . Experiments utilized the following shared facilities at Northwestern University: the Biological Imaging Facility, the Keck Biophysics Facility, the Cell Imaging Facility, the RHLCC Flow Cytometry Facility and the Simpson Querrey Institute for BioNanotechnology. The Biological Imaging Facility is generously supported by the NU Office for Research , and electron microscopy was performed on a JEOL 3200 FETEM purchased with the support of NCRR 1S10RR025092 . The Cell Imaging Facility is generously supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. The RHLCC Flow Cytometry Facility is generously supported by a Cancer Center Support Grant NCI CA060553 . X-ray scattering studies were performed at the DuPont–Northwestern–Dow Collaborative Access Team (DND-CAT) in Sector 5 of the Advanced Photon Source (APS). DND-CAT is supported by E.I. DuPont de Nemours & Co. , The Dow Chemical Company and Northwestern University . Use of the APS, an Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory, was supported by the US DOE under Contract No. DE-AC02-06CH11357 . Also, the authors wish to thank Dr. Matthew Webber for helpful discussion on the CAM assay, Dr. Ricardo Silva for assistance with using DichroWeb, as well as Dr. Eduard Sleep and Dr. Sushant Tripathy for help with HUVEC cell adhesion assay.
Keywords
- Anti-angiogenic
- Maspin
- Peptide amphiphile
- Self-assembly
- g-Helix
ASJC Scopus subject areas
- Molecular Biology
- Biochemistry
- Biotechnology
- Biomedical Engineering
- Biomaterials
