Nanoparticle uptake in tumors is mediated by the interplay of vascular and collagen density with interstitial pressure

Nanoparticle delivery into solid tumors is affected by vessel density, interstitial fluid pressure (IFP) and collagen, as shown here by contrasting the in vivo macroscopic quantitative uptake of 40 nm fluorescent beads in three tumor types. The fluorescence uptake was quantified on individual animals by normalization with the transmitted light and thennormalized to normal tissue uptake in each mouse. Mean data for uptake in individual tumor lines then showed expected trends with the largest uptake in the most vascularized tumor line. Tumor lines with increased collagen were also consistent with highest interstitial fluid pressure, and correlated with lowest uptake of nanoparticles. The data is consistent with a delivery model indicating that while vascular permeability is maximized by neovascular growth, it is inhibited by collagen content and the resulting interstitial pressure. Imaging of these parameters in vivo can lead to better individual non-invasive methods to assess drug penetration in situ