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

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 Bhamidipati, Thomas G. Uhler, Elizabeth D. Hood, Raisa Yu. Kiseleva, Vladimir S. Shuvaev, Tea Shuvaeva, Makan Khoshnejad, Ian Johnston, Jason V. Gregory, Joerg Lahann, Tao Wang, Edward Cantu, William M. Armstead, Samir Mitragotri and Vladimir Muzykantov ()
Additional contact information
Jacob S. Brenner: 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
Priyal Patel: 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

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05079-7

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