Increasing the efficiency of photodynamic therapy by improved light delivery and oxygen supply using an anticoagulant in a solid tumor model

Abstract

The main factors in photodynamic therapy (PDT) are: photosensitizer retention, photon absorption, and oxygen supply. Each factor has its unique set of problems that poses limitation to the treatment. Both light delivery and oxygen supply are significant bottlenecks in PDT. Vascular closure during PDT reduces oxygen supply to the targeted tissue. On the other hand, with the changes in blood perfusion, the tissue optical properties change, and result in variation in irradiation light transmission. For these reasons, it becomes very important to avoid blood coagulation and vascular closure during PDT. The efficiency of PDT combined with the anticoagulant heparin was studied in a BALB/c mouse model with subcutaneous EMT6 mammary carcinomas. Mice were randomized into three groups: control, PDT-only, and PDT with heparin. The photosensitizer Photofrin was used in our experiments. Light transmission, blood perfusion, and local production of reactive oxygen species (ROS) were monitored during the treatment. The corresponding histological examinations were performed to determine the thrombosis immediately after irradiation and to evaluate tumor necrosis 48 hours after the treatment. The results clearly demonstrated that PDT combined with pre-administered heparin can significantly reduce thrombosis during light irradiation. The blood perfusion, oxygen supply, and light delivery are all improved. Improved tumor responses in the combined therapy, as shown with the histological examination and tumor growth assay, are clearly demonstrated and related to an increased local ROS production. Transitory anticoagulation treatment significantly enhances the antitumor effect of PDT. It is mainly due to the improvement of the light delivery and oxygen supply in tumor, and ultimately the amount of ROS produced during PDT.