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Application of a novel boronated porphyrin (H 2 OCP) as a dual sensitizer for both PDT and BNCT
Author(s) -
Hiramatsu Ryo,
Kawabata Shinji,
Miyatake ShinIchi,
Kuroiwa Toshihiko,
Easson Michael W.,
Vicente M. Graça H.
Publication year - 2011
Publication title -
lasers in surgery and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.888
H-Index - 112
eISSN - 1096-9101
pISSN - 0196-8092
DOI - 10.1002/lsm.21026
Subject(s) - photodynamic therapy , porphyrin , chemistry , cytotoxicity , in vivo , radiochemistry , boron , in vitro , nuclear chemistry , cancer research , nuclear medicine , biochemistry , medicine , organic chemistry , microbiology and biotechnology , biology
Abstract 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 (H 2 OCP) is a boronated porphyrin having eight boron clusters linked to the porphyrin ring. To evaluate H 2 OCP'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 2 OCP by measuring the boron concentration over time, and compared the cellular uptake/clearance of boron after exposure to H 2 OCP in conjunction with boronophenylalanine (BPA) and sodium borocaptate (BSH), both of which are currently used in clinical BNCT studies. We evaluated the cytotoxicity of H 2 OCP‐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 H 2 OCP. Results H 2 OCP accumulated within cells to a greater extent than BPA/BSH, and H 2 OCP was retained inside the cells to approximately the same extent as BSH. The cell‐surviving fraction following laser irradiation (8 J/cm 2 , 18 hours after exposure to 10 µg B/ml H 2 OCP) 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 H 2 OCP was clearly demonstrated within the tumor cells by fluorescence microscopy. Conclusions H 2 OCP has been proven to be a promising photosensitizer for PDT. H 2 OCP 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 H 2 OCP could be an effective novel dual sensitizing agent for use in both PDT and BNCT. Lasers Surg. Med. 43:52–58, 2011. © 2011 Wiley‐Liss, Inc.