Phonozen-mediated photodynamic therapy comparing two wavelengths in a mouse model of peritoneal carcinomatosis.

Abstract

This study assessed the therapeutic efficacy of intraperitoneal photodynamic therapy (PDT) using photosensitizer activation at two different wavelengths, 405 and 664nm, in a mouse model of peritoneal carcinomatosis. The dark and light cytotoxicity of chlorin e6-polyvinylpyrrolidone (Phonozen) were measured in vitro under 402 ± 14 and 670 ± 18nm LED activation in bioluminescent human gastric cancer cells, MKN45-luc. Cell viability was measured at 6h after irradiation using the PrestoBlue assay. Corresponding in vivo studies were performed in athymic nude mice by intraperitoneal injection of 1 × 106 MKN45-luc cells. PDT was performed 10 d after tumor induction and comprised intraperitoneal injection of Phonozen followed by light irradiation at 3h, delivered by a diffusing-tip optical fiber placed in the peritoneal cavity and coupled to a 405 or 664nm diode laser to deliver a total energy of 50J (20 mice per cohort). Whole-body bioluminescence imaging was used to track the tumor burden after PDT out to 130days, and 5 mice in each cohort were sacrificed at 4h post treatment to measure the acute tumor necrosis. Photosensitizer dose-dependent photocytotoxicity was higher in vitro at 405 than 664nm. In vivo, PDT reduced the tumor growth rate at both wavelengths, with no statistically significant difference. There was substantial necrosis, and median survival was significantly prolonged at both wavelengths compared with controls (46 and 46 vs. 34 days). Phonozen-mediated PDT results in significant cytotoxicity in vitro as well as tumor necrosis and prolonged survival in vivo following intraperitoneal light irradiation. Blue light was more photocytotoxic than red in vitro and had marginally higher efficacy in vivo.