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

Because of high spatial resolution and superior tissue penetration, a femtosecond laser of the near-infrared spectrum has great potential to improve the efficacy of conventional photodynamic therapy; however, the lack of suitable photosensitizers has so far limited its bedside applications. Recently, our group reported that a brief irradiation by femtosecond lasers in the absence of exogenous probes can modulate various cellular behaviors in vitro and in vivo. Here, we demonstrate that targeted irradiation by a femtosecond laser disrupted tumor-associated blood vessels, and the inhibition of vascular endothelial growth factor signaling augmented the efficacy of laser-induced angiolysis. Further, we show that reactive oxygen species (ROS) are generated in response to laser irradiation, and reducing the intracellular levels of ROS rendered endothelial cells resistant to laser-induced cytotoxicity. Collectively, these results indicate that a femtosecond laser can be used as a vascular-disrupting therapeutic modality for cancer treatment, especially when used in combination with conventional anti-angiogenic therapies. (C) 2011 Elsevier Inc. All rights reserved.