Application of a novel boronated porphyrin (H2OCP) as a dual sensitizer for 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 rat glioma cells. Materials and Methods We examined the time-dependent cellular uptake of H 2OCP 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 Aμg 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. © 2011 Wiley-Liss, Inc.
Publication Source (Journal or Book title)
Lasers in Surgery and Medicine
Hiramatsu, R., Kawabata, S., Miyatake, S., Kuroiwa, T., Easson, M., & Vicente, M. (2011). Application of a novel boronated porphyrin (H2OCP) as a dual sensitizer for both PDT and BNCT. Lasers in Surgery and Medicine, 43 (1), 52-58. https://doi.org/10.1002/lsm.21026