Blockade of vascular endothelial growth factor sensitizes tumor-associated vasculatures to angiolytic therapy with a high-frequency ultrashort pulsed laser

► Irradiation of femtosecond lasers induced dramatic and rapid changes in cellular morphology leading to necrotic cell death by cultured human umbilical vein endothelial cells. ► Focal irradiation with a femtosecond laser can induce endothelial damage even without a photosensitizing agent in normal or tumor vasculatures. ► Tumor-associated vessels are less vulnerable to the femtosecond laser, even though they are structurally and functionally defective. ► VEGFs, probably originating from the tumors, are responsible for the resistance of tumor-associated vasculature to laser-induced cytotoxicity, and blockade of VEGFs signaling can normalize structural abnormalities as well as functional derangement in tumor vessels. ► Reactive oxygen species are involved in the endothelial damage induced by femtosecond lasers.