IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Phototoxic action of a lyphophilic Zn(II) phthalocyanine in colon carcinoms cells
Autor/es:
NICOLÁS CHIARANTE, JULIETA MARIN, MARÍA C. GARCÍA VIOR, ALEJANDRO SOSNIK, JOSEFINA AWRUCH, LEONOR ROGUIN.
Lugar:
Córdoba
Reunión:
Congreso; 16th International Congress on Photobiology; 2014
Institución organizadora:
International Union on Photobiology
Resumen:
PHOTOTOXIC ACTION OF A LYPOPHILIC Zn(II) PHTHALOCYANINE IN COLON CARCINOMA CELLS Nicolás Chiarante1, Julieta Marino1, María C. García Vior2, Alejandro Sosnik3, Josefina Awruch2, Leonor Roguin1. IQUIFIB1, Dpto. de Química Orgánica2, FFyB, UBA, Junín 956, Buenos Aires, Argentina. nchiarante@ffyb.uba.ar Department of Materials Science and Engineering3, Technion-Israel Institute of Technology, Technion City, Haifa, Israel. Phthalocyanines (Pcs) have been found to be useful photosensitizers for photodynamic therapy (PDT) [1-2]. The tendency of Pcs to form aggregates has encouraged the use of nanocarriers that improve their solubility [3]. The aim of this work was to study the photodynamic performance of 2,9(10),16(17),23(24)-tetrakis[(2?dimethylamino)ethylsulfanyl] phthalocyaninatozinc(II) (Pc9) encapsulated into a poloxamine polymeric micelle (T1107) in a murine colon carcinoma cell line (CT26). Pc9-T1107 was found to be cytotoxic after irradiation at 2.8 J.cm-2, being the concentration that inhibited 50% of cell growth (IC50 value) of 11 ± 1 nM. It was also demonstrated that after light exposure of Pc9-loaded cells, the production of reactive oxygen species (ROS) increased in a concentration-dependent manner. In addition, a lower cytotoxic effect was obtained when cells were pretreated with the antioxidant TROLOX. By confocal microscopy, a mainly lysosomal localization of Pc9-T1107 was observed. Furthermore, after cell irradiation, the reduction of the fluorescence emission of a lysosomal probe was evident, suggesting the permeabilization of the lysosomal membrane. In accordance with this result, we also showed a significant increase in the cytosolic amount of the lysosomal enzyme cathepsin D in a time-dependent manner after PDT. The inhibitory activity induced by Pc9-T1107 in cell growth was partially reverted in the presence of pepstatin A, a cathepsin D inhibitor. In conclusion, our results showed that Pc9 is a potent cytotoxic agent for PDT, being cell death probably mediated by the generation of ROS and the release of lysosomal proteases. Acknowledgments. This work was supported by grants from CONICET and Universidad de Buenos Aires, Argentina. [1] R. R. Allison, V. Bagnato, C. Sibata, Future Oncol., 2010, 6, 929. [2] J. Taquet, C. Frochot, V. Manneville, M. Barberi-Heyob, Curr. Med. Chem., 2007, 14, 1673. [3] V.P. Torchilin, Adv. Drug Deliv. Rev., 2006, 58, 1532.