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Red blood cell-hitchhiking boosts delivery of nanocarriers to chosen organs by orders of magnitude

Author

Listed:
  • Jacob S. Brenner

    (University of Pennsylvania
    University of Pennsylvania)

  • Daniel C. Pan

    (University of Pennsylvania)

  • Jacob W. Myerson

    (University of Pennsylvania)

  • Oscar A. Marcos-Contreras

    (University of Pennsylvania)

  • Carlos H. Villa

    (University of Pennsylvania
    University of Pennsylvania)

  • Priyal Patel

    (University of Pennsylvania
    University of Pennsylvania)

  • Hugh Hekierski

    (University of Pennsylvania)

  • Shampa Chatterjee

    (Institute for Environmental Medicine, University of Pennsylvania)

  • Jian-Qin Tao

    (Institute for Environmental Medicine, University of Pennsylvania)

  • Hamideh Parhiz

    (University of Pennsylvania)

  • Kartik Bhamidipati

    (University of Pennsylvania)

  • Thomas G. Uhler

    (University of Pennsylvania)

  • Elizabeth D. Hood

    (University of Pennsylvania)

  • Raisa Yu. Kiseleva

    (University of Pennsylvania)

  • Vladimir S. Shuvaev

    (University of Pennsylvania)

  • Tea Shuvaeva

    (University of Pennsylvania)

  • Makan Khoshnejad

    (University of Pennsylvania)

  • Ian Johnston

    (University of Pennsylvania)

  • Jason V. Gregory

    (University of Michigan)

  • Joerg Lahann

    (University of Michigan)

  • Tao Wang

    (Penn Cardiovascular Institute, University of Pennsylvania)

  • Edward Cantu

    (University of Pennsylvania)

  • William M. Armstead

    (University of Pennsylvania)

  • Samir Mitragotri

    (School of Engineering & Applied Sciences, Harvard University, Wyss Institute)

  • Vladimir Muzykantov

    (University of Pennsylvania)

Abstract

Drug delivery by nanocarriers (NCs) has long been stymied by dominant liver uptake and limited target organ deposition, even when NCs are targeted using affinity moieties. Here we report a universal solution: red blood cell (RBC)-hitchhiking (RH), in which NCs adsorbed onto the RBCs transfer from RBCs to the first organ downstream of the intravascular injection. RH improves delivery for a wide range of NCs and even viral vectors. For example, RH injected intravenously increases liposome uptake in the first downstream organ, lungs, by ~40-fold compared with free NCs. Intra-carotid artery injection of RH NCs delivers >10% of the injected NC dose to the brain, ~10× higher than that achieved with affinity moieties. Further, RH works in mice, pigs, and ex vivo human lungs without causing RBC or end-organ toxicities. Thus, RH is a clinically translatable platform technology poised to augment drug delivery in acute lung disease, stroke, and several other diseases.

Suggested Citation

  • Jacob S. Brenner & Daniel C. Pan & Jacob W. Myerson & Oscar A. Marcos-Contreras & Carlos H. Villa & Priyal Patel & Hugh Hekierski & Shampa Chatterjee & Jian-Qin Tao & Hamideh Parhiz & Kartik Bhamidipa, 2018. "Red blood cell-hitchhiking boosts delivery of nanocarriers to chosen organs by orders of magnitude," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05079-7
    DOI: 10.1038/s41467-018-05079-7
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    Cited by:

    1. Ivan V. Zelepukin & Olga Yu. Griaznova & Konstantin G. Shevchenko & Andrey V. Ivanov & Ekaterina V. Baidyuk & Natalia B. Serejnikova & Artur B. Volovetskiy & Sergey M. Deyev & Andrei V. Zvyagin, 2022. "Flash drug release from nanoparticles accumulated in the targeted blood vessels facilitates the tumour treatment," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. C. Albert & L. Bracaglia & A. Koide & J. DiRito & T. Lysyy & L. Harkins & C. Edwards & O. Richfield & J. Grundler & K. Zhou & E. Denbaum & G. Ketavarapu & T. Hattori & S. Perincheri & J. Langford & A., 2022. "Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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