title: Coupling growth-factor engineering with nanotechnology for therapeutic angiogenesis.
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.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Rituparna
authors.initials: R
authors.lastname: Sinha Roy
authors.forename: Shivani
authors.initials: S
authors.lastname: Soni
authors.forename: Rania
authors.initials: R
authors.lastname: Harfouche
authors.forename: Pooja R
authors.initials: PR
authors.lastname: Vasudevan
authors.forename: Oliver
authors.initials: O
authors.lastname: Holmes
authors.forename: Hugo
authors.initials: H
authors.lastname: de Jonge
authors.forename: Arthur
authors.initials: A
authors.lastname: Rowe
authors.forename: Abhimanyu
authors.initials: A
authors.lastname: Paraskar
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Hentschel
authors.forename: Dimitri
authors.initials: D
authors.lastname: Chirgadze
authors.forename: Tom L
authors.initials: TL
authors.lastname: Blundell
authors.forename: Ermanno
authors.initials: E
authors.lastname: Gherardi
authors.forename: Raghunath A
authors.initials: RA
authors.lastname: Mashelkar
authors.forename: Shiladitya
authors.initials: S
authors.lastname: Sengupta
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D017228:Hepatocyte Growth Factor / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000648:ultrastructure; D036103:Nanotechnology; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D015202:Protein Engineering; D020836:Protein Structure, Quaternary; D015027:Zebrafish
chemical_list: D017228:Hepatocyte Growth Factor