In Vivo Quantification of Nanoparticle Association with Immune Cell Subsets in Blood

Nanoparticles offer great promise for more effective drug delivery. However, their particulate nature typically results in rapid systemic clearance by immune cells in blood. Currently, to understand these interactions, nanoparticle association is probed ex vivo with whole blood. While ex vivo assays give important information about the relative cell association, they do not consider changes in immune cell homeostasis or the complex mixing behavior that occurs in vivo. To address this, a nanoparticle in vivo immune-cell association assay is developed to study the in vivo association of unmodified and poly(ethylene glycol) modified liposomes with immune cells, and compared this to the ex vivo association in static whole blood. In vivo, it is observed that neutrophils play a significantly greater role in nanoparticle binding than suggested by ex vivo assays. The increased influence of neutrophils in vivo is largely due to a significant increase in number of circulating neutrophils after intravenous injection. Conversely, the number of circulating monocytes significantly decreased after intravenous injection, leading to significantly less total association of liposomes to monocytes compared to ex vivo. This novel in vivo immune cell binding assay sheds new light on the fate of nanoparticles following intravenous delivery.