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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Coupling growth-factor engineering with nanotechnology for therapeutic angiogenesis
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Coupling growth-factor engineering with nanotechnology for therapeutic angiogenesis

机译:结合生长因子工程技术与纳米技术治疗血管新生

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摘要

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.
机译:治疗性血管生成是缺血性疾病管理的新兴范例。然而,促血管生成疗法受到当前无法在病理部位持续递送血管生成因子的限制。在这项研究中,我们研究了肝细胞生长因子/散射因子1K1的独特非糖基化活性片段,该片段在体外以及在斑马鱼胚胎和鼠基质胶移植模型中均作为有效的血管生成剂。此外,我们证明了持续释放的纳米制剂1K1暂时改变了通过有丝分裂原激活的蛋白激酶途径的下游信号传导,并放大了血管生成的结果。蛋白质工程和纳米技术的融合为缺血性疾病的治疗提供了令人兴奋的可能性,此外还允许选择性靶向下游信号传导途径,从而转化为离散的表型。

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  • 作者单位

    Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 Harvard-Massachusetts Institute of Technology (MIT) Division of Health Sciences and Technology, Cambridge, MA;

    rnDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 Harvard-Massachusetts Institute of Technology (MIT) Division of Health Sciences and Technology, Cambridge, MA;

    rnDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 Harvard-Massachusetts Institute of Technology (MIT) Division of Health Sciences and Technology, Cambridge, MA;

    rnMassachusetts Institute of Technology, Cambridge, MA;

    rnMedical Research Council MRC Center, Cambridge CB2 2QH, United Kingdom;

    rnMedical Research Council MRC Center, Cambridge CB2 2QH, United Kingdom;

    rnMedical Research Council MRC Center, Cambridge CB2 2QH, United Kingdom;

    rnDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 Harvard-Massachusetts Institute of Technology (MIT) Division of Health Sciences and Technology, Cambridge, MA;

    rnDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;

    rnDepartment of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, England;

    rnDepartment of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, England;

    rnMedical Research Council MRC Center, Cambridge CB2 2QH, United Kingdom;

    rnHarvard-Massachusetts Institute of Technology (MIT) Division of Health Sciences and Technology, Cambridge, MA National Chemical Laboratory, Pune, 411008, India;

    rnDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 Harvard-Massachusetts Institute of Technology (MIT) Division of Health Sciences and Technology, Cambridge, MA;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    HGF/SF; protein engineering; ischemic disease; cardiovascular disease; nanoparticle;

    机译:HGF / SF;蛋白质工程;缺血性疾病心血管疾病;纳米粒子;

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