Photofrin and indocyanine green-mediated photodynamic therapy in cancer treatment

Abstract

Photodynamic therapy (PDT) is a minimally invasive therapeutic approach for clinical treatment of cancer. PDT-mediated oxidative stress leads to cell death and can elicit the expression of genes associated with cell survival, such as AKT/protein kinase B. Phosphorylation and subsequent activation of AKT induces a survival response. For the rst time in literature, our results from in vitro and in vivo experiments demonstrated that PDT treatments mediated by excitation of Photofrin with a 630-nm diode laser induced AKT phosphorylation. PDT-mediated AKT pathway activation may stimulate cell survival in remaining tumor tissue leading to tumor reoccurrence, therefore, inhibiting PDT-mediated AKT activation may improve treatment responsiveness. Our ndings demonstrated that, minimally toxic AKT inhibitor, PI- 103, e ectively inhibited PDT-mediated AKT phosphorylation both in vitro and in vivo. These results have great importance in relevance to development of combinatorial therapies using PDT and PI-103 inhibitor to improve treatment responsiveness. Indocyanine Green (ICG) exhibits maximum absorption at around 800 nm, which is an advantage for its use in treatment of deeper tumors. In this study, an 809 nm diode laser was designed and custom manufactured in our laboratory to investigate the e ects of ICG-mediated PDT on human breast cancer cells. This study for the rst time reported that ICG-PDT application exhibited strong and stable phototoxic e ects on MDA-MB231 breast cancer cells. Collectively, these novel ndings presented in this thesis study contributed largely to the knowledge of PDT in cancer treatment, which is the rst reported PDT study in Turkey, and open new research areas for further investigations.|Keywords: AKT, ICG, PDT, Photofrin, 630 nm diode laser, 809 nm diode laser.