Comparative characterization of the efficiency and cellular pharmacokinetics of Foscan®- and Foslip®-based photodynamic treatment in human biliary tract cancer cell lines

Abstract

Due to the poor prognosis and limited management options for perihilar cholangiocarcinoma (CC) the development of alternatives for treatment is an important topic. Photodynamic therapy (PDT) with porfimer as palliative or neoadjuvant endoscopic treatment of non-resectable perihilar CC has improved quality of life and survival time, but cannot eradicate the primary tumors because of inadequate tumoricidal depth (4 mm only around the tumor stenoses). The use of meta-tetrahydroxyphenyl chlorin (mTHPC) and photoactivation at higher wavelengths (650–660 nm) provides high tumoricidal depth (10 mm) for PDT of pancreatic cancer and should yield similar tumoricidal depth in CC. This study investigates the photodynamic characteristics of mTHPC in solvent-based formulation (Foscan®) and in liposomal (water soluble) formulation (Foslip®) in an in vitro model system consisting of two biliary cancer cell lines (GBC, gall bladder cancer and BDC, bile duct cancer cells). Dark toxicity, photodynamic efficiency, time-dependent uptake and retention and intracellular localization of Foscan® and Foslip® were studied. The results prove mTHPC as a potent photosensitizing agent with high phototoxic potential in biliary cancer cells as a concentration of 600 ng ml^–1 and irradiation with 1.5 J cm^–2 (660 ± 10 nm) is sufficient for about 90% cell killing. Addition of foetal bovine serum (FBS) to the incubation medium and analysis of the uptake and phototoxic properties reveals that both photosensitizer formulations bind to serum protein fractions, i.e. no difference between Foscan® and Foslip® can be found in the presence of FBS. Laser scanning fluorescence microscopy indicates a similar pattern of perinuclear localization of both sensitizers. This study demonstrates the potential of mTHPC for treatment of bile duct malignancies and provides evidence that Foslip® is an equivalent water-soluble formulation of mTHPC that should ease intravenous application and thus clinical use of mTHPC.