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

Nat Commun. 2018 Jul 11;9(1):2684. doi: 10.1038/s41467-018-05079-7.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adsorption
  • Animals
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry*
  • Drug Carriers / pharmacokinetics
  • Drug Delivery Systems / methods*
  • Erythrocytes / chemistry*
  • Humans
  • Lung / metabolism
  • Lung Diseases / metabolism
  • Lung Diseases / therapy
  • Mice, Inbred C57BL
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Rats
  • Swine

Substances

  • Drug Carriers