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.

Details

Title
Red blood cell-hitchhiking boosts delivery of nanocarriers to chosen organs by orders of magnitude
Author
Brenner, Jacob S 1   VIAFID ORCID Logo  ; Pan, Daniel C 2 ; Myerson, Jacob W 2   VIAFID ORCID Logo  ; Marcos-Contreras, Oscar A 2 ; Villa, Carlos H 3   VIAFID ORCID Logo  ; Patel, Priyal 1 ; Hekierski, Hugh 4 ; Chatterjee, Shampa 5 ; Jian-Qin, Tao 5 ; Parhiz, Hamideh 2 ; Bhamidipati, Kartik 2 ; Uhler, Thomas G 2 ; Hood, Elizabeth D 2 ; Raisa Yu Kiseleva 2   VIAFID ORCID Logo  ; Shuvaev, Vladimir S 2 ; Shuvaeva, Tea 2 ; Makan Khoshnejad 2 ; Johnston, Ian 2 ; Gregory, Jason V 6 ; Lahann, Joerg 6 ; Wang, Tao 7   VIAFID ORCID Logo  ; Cantu, Edward 8 ; Armstead, William M 4 ; Mitragotri, Samir 9 ; Muzykantov, Vladimir 2 

1  Pulmonary, Allergy, & Critical Care Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Systems Pharmacology and Translational Therapeutics and Center for Translational Targeted Therapeutics and Nanomedicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA 
2  Department of Systems Pharmacology and Translational Therapeutics and Center for Translational Targeted Therapeutics and Nanomedicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA 
3  Department of Systems Pharmacology and Translational Therapeutics and Center for Translational Targeted Therapeutics and Nanomedicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Division of Transfusion Medicine and Therapeutic Pathology, Department of Pathology, University of Pennsylvania, Philadelphia, PA, USA 
4  Department of Anesthesiology & Critical Care, University of Pennsylvania, Philadelphia, PA, USA 
5  Institute for Environmental Medicine, University of Pennsylvania, Philadelphia, PA, USA 
6  Department of Chemical Engineering and Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA 
7  Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA 
8  Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, PA, USA 
9  School of Engineering & Applied Sciences, Harvard University, Wyss Institute, Cambridge, MA, USA 
Pages
1-14
Publication year
2018
Publication date
Jul 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-05079-7
ProQuest document ID
2068344095
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.