UNLABELLED

Metastasis is the main killer in cancer; consequently, there is great interest in novel approaches to prevent and treat metastatic disease. Brain metastases are particularly deadly, as the protection of the blood-brain barrier obstructs the passage of common anticancer drugs. This study used magnetic resonance imaging (MRI) to investigate the therapeutic effects of nanoparticles coated with a tumor-penetrating peptide (iRGD) against a preclinical model of breast cancer brain metastasis. Single doses of iRGD nanoparticle were administered intravenously, and the effect on tumor growth was observed over time. iRGD nanoparticles, when applied in the early stages of metastasis development, strongly inhibited tumor progression. Overall, this study demonstrated for the first time that a single dose of iRGD nanoparticle can have a significant effect on metastatic tumor progression and nonproliferative cancer cell retention when applied early in course of tumor development. These data suggest that iRGD nanoparticles may be useful in preventatively reducing metastasis after a cancer diagnosis has been established.

KEY MESSAGES

bSSFP MRI can be used to track nonproliferative iron-labeled cells and tumor development over time. iRGD-NW, when applied early, has a significant effect on metastatic tumor progression. Retained signal voids represent a subpopulation of nonproliferating tumor cells. Reduced cell retention and tumor burden show a role for iRGD-NW in metastasis prevention. iRGD target is universally expressed; thus, iRGD-NW should be clinically translatable.