Ionizing radiation increases systemic nanoparticle tumor accumulation

Nanoparticle-based therapies are currently being explored for both the imaging and treatment of primary and metastatic cancers. Effective nanoparticle cancer therapy requires significant accumulations of nanoparticles within the tumor environment. Various techniques have been used to improve tumor nanoparticle uptake and biodistribution. Most notable of these techniques is the use of tumor-specific peptide-conjugated nanoparticles and chemical modification of the nanoparticles with immune-evading polymers. Another strategy for improving the tumor uptake of the nanoparticles is modification of the tumor microenvironment with a goal of intensifying the enhanced permeability and retention effect inherent to solid tumors. We demonstrate a twofold increase in the tumor accumulation of systemically delivered iron oxide nanoparticles following a single 15-Gy radiation dose in a syngeneic mouse breast tumor model. This increase in nanoparticle tumor accumulation correlates with a radiation-induced decrease in tumor interstitial pressure and a subsequent increase in vascular permeability. From the Clinical Editor: Targeted delivery of nanoparticles is typically accomplished by functionalized nanoparticles "recognizing" their target. However, modification of the target environment offers another possibility for targeted delivery, as demonstrated in this paper: by applying low-dose radiation to the tumor and administering systemic nanoparticles thereafter, the authors demonstrate a two-fold increase in nanoparticle accumulation.