Therapeutic enhancement of vascular-targeted photodynamic therapy by inhibiting proteasomal function.

Vascular-targeted photodynamic therapy (vPDT) is a novel vascular targeting modality based on site-directed delivery of a photosensitizer to tumor vasculature, which induces reactive oxygen species (ROS)-mediated vascular effects upon light activation. To enhance the therapeutic outcome of vPDT, we combined proteasomal inhibitor bortezomib and vPDT using photosensitizer verteporfin in the present study. We found that bortezomib in combination with verteporfin-PDT induced more accumulation of ubiquitinated proteins and apoptosis in endothelial cells than each individual treatment. The combination therapy also enhanced vPDT-induced inhibition in tumor growth. These results indicate that bortezomib can be used together with verteporfin-PDT for enhanced treatment outcome.