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Exosome Encased Spherical Nucleic Acid Gold Nanoparticle Conjugates as Potent MicroRNA Regulation Agents

Authors

  • Ali H. Alhasan,

    1. Department of Chemistry and International, Institute for Nanotechnology, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208–3113, USA
    2. Interdepartmental Biological Sciences Program, Northwestern University, 2205 Tech Drive, Evanston, IL, 60208–3113, USA
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  • Pinal C. Patel,

    1. AuraSense Therapeutics, LLC, 8045 Lamon Avenue, Suite 410, Skokie, IL, 60077
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  • Chung Hang J. Choi,

    1. Department of Chemistry and International, Institute for Nanotechnology, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208–3113, USA
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  • Chad A. Mirkin

    Corresponding author
    1. Department of Chemistry and International, Institute for Nanotechnology, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208–3113, USA
    • Department of Chemistry and International, Institute for Nanotechnology, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208–3113, USA.

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Abstract

Exosomes are a class of naturally occurring nanomaterials that play crucial roles in the protection and transport of endogenous macromolecules, such as microRNA and mRNA, over long distances. Intense effort is underway to exploit the use of exosomes to deliver synthetic therapeutics. Herein, transmission electron microscopy is used to show that when spherical nucleic acid (SNA) constructs are endocytosed into PC-3 prostate cancer cells, a small fraction of them (<1%) can be naturally sorted into exosomes. The exosome-encased SNAs are secreted into the extracellular environment from which they can be isolated and selectively re-introduced into the cell type from which they were derived. In the context of anti-miR21 experiments, the exosome-encased SNAs knockdown miR-21 target by approximately 50%. Similar knockdown of miR-21 by free SNAs requires a ≈3000-fold higher concentration.

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