Effects of Photodynamic Therapy in Combination with Anti-Angiogenic Drugs on the Chicken Chorioallantoic Membrane Model
Photodynamic therapy (PDT) is clinically-approved in the treatment of angiogenic disorders, particularly eye diseases such as age-related macular degeneration (AMD) and skin cancers, such as basal cell carcinoma. PDT causes vascular occlusion resulting in hypoxia and inflammation, which induces the activation of the hypoxia inducible factors and the release of vascular endothelial growth factor, amongst other pro-angiogenic factors. This leads to the activation angiogenic pathways and the biological response of revascularization of treated areas. Therefore, the use of PDT in combination with anti-angiogenic strategies could increase treatment efficiency for diseases such as AMD by extending the photodynamic angio-occlusive effects. The aim of this research is to compare the effectiveness of Visudyne®-PDT in combination with one of two drugs targeting angiogenesis through different mechanisms: 1) direct targeting of VEGF, the clinically targeted pathway in AMD, by means of the antibody Avastin®, and 2) blocking the angiogenic signaling pathway with a receptor tyrosine kinase inhibitor, Sutent®. These compounds were tested on the chicken chorioallantoic membrane (CAM) with and without PDT. When drugs were topically applied during early stages of embryonic development to inhibit physiological angiogenesis, fifty percent inhibition (ED50) is seen at 45 and 200 μM for Avastin® and Sutent®, respectively. To study the effects of drug inhibition on an induced angiogenic state, closure of small blood vessels is achieved through Visudyne®-PDT. Vascular regrowth following photodamage is significantly inhibited by both drugs, with an ED50 of 7 and 17 μM for Avastin® and Sutent®, respectively. These results suggest the therapeutic potential of the tyrosine kinase inhibitor for application in combination with PDT strategies. The use of small molecule drugs could lead to more optimal application of anti-angiogenic compounds via droplets or slow-release drug delivery systems.
Laboratory of The Medical Photonics Group, EPFL. - External expert: Arjan W. Griffioen, Department of Medical Oncology VU University Medical Center, Amsterdam, The Netherland
Record created on 2012-01-03, modified on 2016-08-09