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Integrating Novel Protein Engineering and Nanotechnology for Therapeutic Angiogenesis
Author(s) -
Roy Rituparna Sinha,
Soni Shivani,
Harfouche Rania,
Vasudevan Pooja R,
Paraskar Abhimanyu,
Sengupta Shiladitya
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb518
Subject(s) - angiogenesis , therapeutic angiogenesis , in vivo , hepatocyte growth factor , mapk/erk pathway , cancer research , chemistry , microbiology and biotechnology , nanotechnology , signal transduction , receptor , materials science , biology , neovascularization , biochemistry
Therapeutic angiogenesis is an emerging concept that can potentially be harnessed for management of ischemic pathologies. Hepatocyte growth factor/scatter factor (HGF/SF) promotes angiogenesis but the native protein has limited therapeutic potential due to its complex multidomain structure with glycosylation sites. To address this translational challenge, a novel spliced HGF/SF variant, 1K1 encoding the N‐terminal domain and first kringle (K1) domain was engineered with reverse mutations (K132E:R134E) introduced in the K1 domain. To address the clinical requirement of sustained delivery, 1K1 was formulated in a polymeric nanoparticle of 60–140 nm size and with the total loading efficiency 54.27±7.12%. 1K1‐nanoparticle (NP) induced significantly greater angiogenesis both in vitro and in vivo than free 1K1 (P<0.05). 1K1‐NP induced angiogenesis were blocked by PHA665752, LY294002 and PD98059 inhibitors in a concentration‐dependent manner (P<0.05), suggesting that 1K1‐NP induces angiogenesis through MET receptor and downstream MAPK and PI3K pathways. Integrating novel protein engineering strategy and nanotechnology offer stimulating revascularization at the site of ischemic pathology.