BACKGROUND AND OBJECTIVE: Boronated porphyrins have emerged as promising dual sensitizers for use in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by virtue of their known tumor affinity, low cytotoxicity in dark conditions, and easy synthesis with high boron content. Octa-anionic 5,10,15,20-tetra[3,5-(nido-carboranylmethyl)phenyl] porphyrin (H₂OCP) is a boronated porphyrin having eight boron clusters linked to the porphyrin ring. To evaluate H₂OCP's applicability to both PDT and BNCT, we performed an in vitro and ex vivo study using F98 rat glioma cells. MATERIALS AND METHODS: We examined the time-dependent cellular uptake of H₂OCP by measuring the boron concentration over time, and compared the cellular uptake/clearance of boron after exposure to H₂OCP in conjunction with boronophenylalanine (BPA) and sodium borocaptate (BSH), both of which are currently used in clinical BNCT studies. We evaluated the cytotoxicity of H₂OCP-mediated PDT using a colony-forming assay and assessed the tumorigenicity of the implantation of pre-treated cells using Kaplan-Meier survival curves. Fluorescence microscopy was also performed to evaluate the cellular uptake of H₂OCP. RESULTS: H₂OCP accumulated within cells to a greater extent than BPA/BSH, and H₂OCP was retained inside the cells to approximately the same extent as BSH. The cell-surviving fraction following laser irradiation (8 J/cm², 18 hours after exposure to 10 µg B/ml H₂OCP) was <0.05. The median survival times of the pre-treated cell-implanted rats were longer than those of the untreated group (P < 0.05). The fluorescence of H₂OCP was clearly demonstrated within the tumor cells by fluorescence microscopy. CONCLUSIONS: H₂OCP has been proven to be a promising photosensitizer for PDT. H₂OCP has also been proposed as a potentially effective replacement of BPA or BSH, or as a replacement of both BPA/BSH. Our study provides more evidence that H₂OCP could be an effective novel dual sensitizing agent for use in both PDT and BNCT.
BACKGROUND AND OBJECTIVE:Boronated porphyrins have emerged as promising dual sensitizers for use in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by virtue of their known tumor affinity, low cytotoxicity in dark conditions, and easy synthesis with high boron content. Octa-anionic 5,10,15,20-tetra[3,5-(nido-carboranylmethyl)phenyl] porphyrin (H₂OCP) is a boronated porphyrin having eight boron clusters linked to the porphyrin ring. To evaluate H₂OCP's applicability to both PDT and BNCT, we performed an in vitro and ex vivo study using F98 ratglioma cells. MATERIALS AND METHODS: We examined the time-dependent cellular uptake of H₂OCP by measuring the boron concentration over time, and compared the cellular uptake/clearance of boron after exposure to H₂OCP in conjunction with boronophenylalanine (BPA) and sodium borocaptate (BSH), both of which are currently used in clinical BNCT studies. We evaluated the cytotoxicity of H₂OCP-mediated PDT using a colony-forming assay and assessed the tumorigenicity of the implantation of pre-treated cells using Kaplan-Meier survival curves. Fluorescence microscopy was also performed to evaluate the cellular uptake of H₂OCP. RESULTS: H₂OCP accumulated within cells to a greater extent than BPA/BSH, and H₂OCP was retained inside the cells to approximately the same extent as BSH. The cell-surviving fraction following laser irradiation (8 J/cm², 18 hours after exposure to 10 µg B/ml H₂OCP) was <0.05. The median survival times of the pre-treated cell-implanted rats were longer than those of the untreated group (P < 0.05). The fluorescence of H₂OCP was clearly demonstrated within the tumor cells by fluorescence microscopy. CONCLUSIONS: H₂OCP has been proven to be a promising photosensitizer for PDT. H₂OCP has also been proposed as a potentially effective replacement of BPA or BSH, or as a replacement of both BPA/BSH. Our study provides more evidence that H₂OCP could be an effective novel dual sensitizing agent for use in both PDT and BNCT.
Authors: J A Coderre; T M Button; P L Micca; C D Fisher; M M Nawrocky; H B Liu Journal: Int J Radiat Oncol Biol Phys Date: 1994-10-15 Impact factor: 7.038
Authors: Arthur B Volovetsky; Vladimir S Sukhov; Irina V Balalaeva; Varvara V Dudenkova; Natalia Yu Shilyagina; Аlexey V Feofanov; Anastasija V Efremenko; Mikhail A Grin; Andrey F Mironov; Igor B Sivaev; Vladimir I Bregadze; Anna V Maslennikova Journal: Int J Mol Sci Date: 2017-11-28 Impact factor: 5.923