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Lipid-Like Nanoparticles for Small Interfering RNA Delivery to Endothelial Cells

Authors

  • Seung-Woo Cho,

    1. Department of Chemical Engineering Massachusetts Institute of Technology 77 Massachusetts Avenue, Cambridge, MA 02139 (USA)
    2. Department of Anesthesiology Children′s Hospital Boston Harvard Medical School 300 Longwood Avenue, Boston, MA 02115 (USA)
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  • Michael Goldberg,

    1. Department of Chemistry Massachusetts Institute of Technology 77 Massachusetts Avenue, Cambridge, MA 02139 (USA)
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  • Sun Mi Son,

    1. Department of Chemical Engineering Massachusetts Institute of Technology 77 Massachusetts Avenue, Cambridge, MA 02139 (USA)
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  • Qiaobing Xu,

    1. Department of Chemical Engineering Massachusetts Institute of Technology 77 Massachusetts Avenue, Cambridge, MA 02139 (USA)
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  • Fan Yang,

    1. Department of Chemical Engineering Massachusetts Institute of Technology 77 Massachusetts Avenue, Cambridge, MA 02139 (USA)
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  • Ying Mei,

    1. Department of Chemical Engineering Massachusetts Institute of Technology 77 Massachusetts Avenue, Cambridge, MA 02139 (USA)
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  • Said Bogatyrev,

    1. Department of Chemical Engineering Massachusetts Institute of Technology 77 Massachusetts Avenue, Cambridge, MA 02139 (USA)
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  • Robert Langer,

    1. Department of Chemical Engineering Massachusetts Institute of Technology 77 Massachusetts Avenue, Cambridge, MA 02139 (USA)
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  • Daniel G. Anderson

    Corresponding author
    1. David H. Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology 45 Carleton Street, E25-342, Cambridge, MA 02142 (USA)
    • David H. Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology 45 Carleton Street, E25-342, Cambridge, MA 02142 (USA).
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Abstract

Here, nanoparticles composed of lipid-like materials (lipidoids) to facilitate non-viral delivery of small interfering RNA (siRNA) to endothelial cells (ECs) are developed. Nanoparticles composed of siRNA and lipidoids with small size (∼200 nm) and positive charge (∼34 mV) are formed by self-assembly of lipidoids and siRNA. Ten lipidoids are synthesized and screened for their ability to facilitate the delivery of siRNA into ECs. Particles composed of leading lipidoids show significantly better delivery to ECs than a leading commercially available transfection reagent, Lipofectamine 2000. As a model of potential therapeutic application, nanoparticles composed of the top performing lipidoid, NA114, are studied for their ability to deliver siRNA targeting anti-angiogenic factor (SHP-1) to human ECs. Silencing of SHP-1 expression significantly enhances EC proliferation and decreases EC apoptosis under a simulated ischemic condition.

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