The use of nanoparticles as
tumor-targeting agents is steadily increasing, and the influence of nanoparticle characteristics such as size and stealthiness have been established for a large number of nanocarrier systems. However, not much is known about the impact of
tumor presence on nanocarrier circulation times. This paper reports on the influence of
tumor presence on the in vivo circulation time and biodistribution of
polybutadiene-
polyethylene oxide (PBd-PEO) polymersomes. For this purpose, polymersomes were loaded with the gamma-emitter 111In and administered intravenously, followed by timed ex vivo biodistribution. A large reduction in circulation time was observed for
tumor-bearing mice, with a circulation half-life of merely 5 min (R2 = 0.98) vs 117 min (R2 = 0.95) in healthy mice. To determine whether the rapid polymersome clearance observed in
tumor-bearing mice was mediated by macrophages, chlodronate
liposomes were administered to both healthy and
tumor-bearing mice prior to the
intravenous injection of radiolabeled polymersomes to deplete their macrophages. Pretreatment with chlodronate
liposomes depleted macrophages in the spleen and liver and restored the circulation time of the polymersomes with no significant difference in circulation time between healthy mice and
tumor-bearing mice pretreated with
clodronate liposomes (15.2 ± 1.2% ID/g and 13.6 ± 2.7% ID/g, respectively, at 4 h p.i. with p = 0.3). This indicates that activation of macrophages due to
tumor presence indeed affected polymersome clearance rate. Thus, next to particle design, the presence of a
tumor can also greatly impact circulation times and should be taken into account when designing studies to evaluate the distribution of polymersomes.