Novel bacteriochlorine for high tissue-penetration: photodynamic properties in human biliary tract cancer cells in vitro and in a mouse tumour model

Abstract

Photodynamic therapy of bile duct cancer using hematoporphyrin derivative (HPD) and laser light of 630 nm wavelength is confined to a tumouricidal tissue penetration of 4 mm, which might be doubled with laser light between 700 and 800 nm. Therefore, we investigated the photosensitising properties of a novel bacteriochlorine, tetrakis-pyridyl-tetrahydroporphyrin tosylat (THP) with high absorption at 763 nm. Two biliary cancer cell lines (BDC, GBC) were incubated with HPD or THP to assess cellular uptake kinetics, dark cytotoxicity, and photodynamic cytotoxicity (laser light exposure 1–20 J/cm 2). Tumours grown from BDC cells in subcutaneous tissue of severe combined immunodeficient mice were treated with laser light of 30 J/cm 2 after injection of THP. The concentrations that killed 50% of cells in the dark were 680 μg/ml of HPD, but >6400 μg/ml of THP in BDC cells, and 220 μg/ml of HPD, but 6400 μg/ml of THP in GBC cells. Both cell lines exhibited uptake and retention of THP and photodynamic cytotoxicity (up to 86% cells killed). THP induced tumour-selective phototoxicity in the cholangiocarcinoma model. The novel bacteriochlorine THP exhibits photosensitiser properties in biliary tract cancer cells in vitro and in vivo and could achieve deep tumouricidal tissue penetration due to photoactivation at 763 nm.