PUBLICATION
Coupling growth-factor engineering with nanotechnology for therapeutic angiogenesis
- Authors
- Sinha Roy, R., Soni, S., Harfouche, R., Vasudevan, P.R., Holmes, O., de Jonge, H., Rowe, A., Paraskar, A., Hentschel, D.M., Chirgadze, D., Blundell, T.L., Gherardi, E., Mashelkar, R.A., and Sengupta, S.
- ID
- ZDB-PUB-100726-6
- Date
- 2010
- Source
- Proceedings of the National Academy of Sciences of the United States of America 107(31): 13608-13613 (Journal)
- Registered Authors
- Hentschel, Dirk, Sengupta, Shiladitya
- Keywords
- HGF/SF, protein engineering, ischemic disease, cardiovascular disease, nanoparticle
- MeSH Terms
-
- Alternative Splicing
- Amino Acid Sequence
- Animals
- Cells, Cultured
- Disease Models, Animal
- Hepatocyte Growth Factor/chemistry
- Hepatocyte Growth Factor/genetics
- Hepatocyte Growth Factor/therapeutic use*
- Humans
- Mice
- Microscopy, Electron, Transmission
- Models, Molecular
- Molecular Sequence Data
- Nanoparticles/ultrastructure
- Nanotechnology*
- Neovascularization, Pathologic/drug therapy*
- Neovascularization, Physiologic/drug effects
- Protein Engineering
- Protein Structure, Quaternary
- Zebrafish
- PubMed
- 20639469 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Sinha Roy, R., Soni, S., Harfouche, R., Vasudevan, P.R., Holmes, O., de Jonge, H., Rowe, A., Paraskar, A., Hentschel, D.M., Chirgadze, D., Blundell, T.L., Gherardi, E., Mashelkar, R.A., and Sengupta, S. (2010) Coupling growth-factor engineering with nanotechnology for therapeutic angiogenesis. Proceedings of the National Academy of Sciences of the United States of America. 107(31):13608-13613.
Abstract
Therapeutic angiogenesis is an emerging paradigm for the management of ischemic pathologies. Proangiogenic Therapy is limited, however, by the current inability to deliver angiogenic factors in a sustained manner at the site of pathology. In this study, we investigated a unique nonglycosylated active fragment of hepatocyte growth factor/scatter factor, 1K1, which acts as a potent angiogenic agent in vitro and in a zebrafish embryo and a murine matrigel implant model. Furthermore, we demonstrate that nanoformulating 1K1 for sustained release temporally alters downstream signaling through the mitogen activated protein kinase pathway, and amplifies the angiogenic outcome. Merging protein engineering and nanotechnology offers exciting possibilities for the treatment of ischemic disease, and furthermore allows the selective targeting of downstream signaling pathways, which translates into discrete phenotypes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping