Nanoparticle Accumulation in Angiogenic Tissues: Towards Predictable Pharmacokinetics

Nanoparticles are increasingly used in medical applications such as drug delivery, imaging, and biodiagnostics, particularly for cancer. The design of nanoparticles for tumor delivery has been largely empirical, owing to a lack of quantitative data on angiogenic tissue sequestration. Using fluorescence correlation spectroscopy, the deposition rate constants of nanoparticles into angiogenic blood vessel tissue are determined. It is shown that deposition is dependent on surface charge. Moreover, the size dependency strongly suggests that nanoparticles are taken up by a passive mechanism that depends largely on geometry. These findings imply that it is possible to tune nanoparticle pharmacokinetics simply by adjusting nanoparticle size. Nanoparticles circulating in angiogenic blood vessels will partition into surrounding tissues through fenestrations in the blood vessel walls. This partitioning depends on nanoparticle properties such as surface charge and size. The size dependence of partitioning rates found here suggests that the mechanism is largely controlled by geometry. Thus, the angiogenic blood vessels function like a size exclusion filter.