Many precision medicines, such as kinase inhibitors, must reach tumors at relatively high concentrations to achieve a therapeutic response. Disseminated tumors, however, are poorly accessible to nanoscale drug delivery systems because of the vascular barrier, which attenuates extravasation at the tumor site. We synthesized fucosylated polysaccharide-based nanomaterials to bind a new target to localize personalized drugs to the tumor microenvironment to obviate dose-limiting toxicities and concomitantly improve therapeutic index. P-selectin, a molecule expressed on activated vasculature that facilitates metastasis by arresting tumor cells at the endothelium, was studied for its potential to use the same mechanism to arrest nanomedicines at the tumor vessels. We found that the nanoparticles targeted MEK and PI3K inhibitors to tumor sites in both primary and metastatic models, resulting in superior anti-tumor efficacy and the striking reduction of toxicities. In tumors devoid of P-selectin, we found that ionizing radiation guided the nanoparticles to the disease site by inducing P-selectin expression, suggesting a potential strategy to target disparate drug classes to almost any solid tumor.<br/>

Targeting precision nanomedicines to the tumor microenvironment

254th National Meeting (2017)

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