Journal
ACS NANO
Volume 7, Issue 12, Pages 11129-11137Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nn404853z
Keywords
hitchhiking; cell-mediated drug delivery; nanomedicine; nanotechnology
Categories
Funding
- National Science Foundation Graduate Research Fellowship [DGE-1144085]
- MRSEC Program of the NSF [DMR 1121053]
- NIH [HL087036, HL090697, HL121134]
- NSF
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Nanoparticulate drug delivery systems are one of the most widely investigated approaches for developing novel therapies for a variety of diseases. However, rapid clearance and poor targeting limit their clinical utility. Here, we describe an approach to harness the flexibility, circulation, and vascular mobility of red blood cells (RBCs) to simultaneously overcome these limitations (cellular hitchhiking). A noncovalent attachment of nanoparticles to RBCs simultaneously increases their level in blood over a 24 h period and allows transient accumulation in the lungs, while reducing their uptake by liver and spleen. RBC-adsorbed nanoparticles exhibited similar to 3-fold increase in blood persistence and similar to 7-fold higher accumulation in lungs. RBC-adsorbed nanoparticles improved lung/liver and lung/spleen nanoparticle accumulation by over 15-fold and 10-fold, respectively. Accumulation in lungs is attributed to mechanical transfer of particles from the RBC surface to lung endothelium. Independent tracing of both nanoparticles and RBCs in vivo confirmed that RBCs themselves do not accumulate in lungs. Attachment of anti-ICAM-1 antibody to the exposed surface of NPs that were attached to RBCs led to further increase in lung targeting and retention over 24 h. Cellular hitchhiking onto RBCs provides a new platform for improving the blood pharmacokinetics and vascular delivery of nanoparticles while simultaneously avoiding uptake by liver and spleen, thus opening the door for new applications.
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