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

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 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. 2018. “Red blood cell-hitchhiking boosts delivery of nanocarriers to chosen organs by orders of magnitude.” Nat Commun, 9, 1, Pp. 2684.

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.