Abstract:

High Z gold nanoparticles generate photoelectrons or Auger electrons when irradiated by low energy (<150 keV) x-ray photons leading to dose amplification. These nanoparticles can be targeted to the tumor vasculature using αvβ3, which is overexpressed on tumors and tumor endothelial cells but under expressed in healthy tissue, leading to vascular disruption. A vascular disruption approach allows for a multi-pronged treatment including local dose amplification, increased drug permeation, and tumor microenvironment immunostimulation. In vitro and in vivo studies with human lung adenocarcinoma and murine triple negative breast cancer were conducted to understand the effects of vascular disruption therapy. Studies confirmed an increase in permeation relative to drug molecular weight as well as improved microenvironment immune cell penetration post-therapy. An approach to improve permeation as well as transition TNBC from a “cold” to a “hot” tumor would be a major step forward to improving current treatments as well as open doors for upcoming therapies