Coupling growth-factor engineering with nanotechnology for therapeutic angiogenesis.
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.
Sinha Roy
Rituparna
R
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Soni
Shivani
S
Harfouche
Rania
R
Vasudevan
Pooja R
PR
Holmes
Oliver
O
de Jonge
Hugo
H
Rowe
Arthur
A
Paraskar
Abhimanyu
A
Hentschel
Dirk M
DM
Chirgadze
Dimitri
D
Blundell
Tom L
TL
Gherardi
Ermanno
E
Mashelkar
Raghunath A
RA
Sengupta
Shiladitya
S
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
D017228:Hepatocyte Growth Factor