Porphyrin-Fullerene C60 Dyads with High Ability to Form Photoinduced Charge-Separated State as Novel Sensitizers for Photodynamic Therapy.

M.E.MILANESIO, M.G.ALVAREZ, J.J.SILVER, V.RIVAROLA, E.N.DURANTINI

PHOTOCHEMISTRY AND PHOTOBIOLOGY

American Society for Photobiology

Lugar: Augusta, USA; Año: 2005 vol. 81 p. 891 - 897

0031-8655

  The photodynamic activities of a porphyrin-C60 dyad (P-C60) and its metal complex with Zn(II) (ZnP-C60) were compared with 5-(4-acetamidophenyl)-10,15,20-tris(4-methoxyphenyl)porphyrin (P), both in homogeneous medium bearing photooxidizable substrates and in vitro on Hep-2 human larynx carcinoma cell line. This study represents the first evaluation of dyads, with high capacity to form photoinduced charge-separated state, to act as agent to inactivate cells by photodynamic therapy (PDT). Absorption and fluorescence spectroscopic studies were performed in toluene and N,N-dimethylformamide (DMF). The emission of the porphyrin moiety in the dyads is strongly quenched by the attached fullerene C60 moiety. The singlet molecular oxygen, O2(1Dg), productions (FD) were determined using 9,10-dimethylanthracene (DMA). The values of FD were strongly dependent of the solvents polarity. Comparable FD values were found for dyads and P in toluene, while O2(1Dg) production was significantly diminished for the dyads in DMF. In more polar solvent, the stabilization of charge-transfer state takes place, decreasing the efficiency of porphyrin triplet state formation. Also, both dyads photosensitize the decomposition of L-tryptophan in DMF. In biological medium, no dark cytotoxicity was observed using sensitizer concentrations ¡Ü1 mM and 24 h of incubation. The uptake of sensitizers into Hep-2 was studied using 1 mM of sensitizer and different times of incubation. Under these conditions, a value of ~1.5 nmol/106 cells was found between 4 and 24 h of incubation. The cell survival after irradiation of the cells with visible light was dependent upon light exposure level. A higher photocytotoxic effect was observed for P-C60, which inactivates 80 % of cells after 15 min of irradiation. Moreover, both dyads keep a high photoactivity even under argon atmosphere. Thus, depending on the microenvironment where the sensitizer is localized, these compound could produce a biological photodamage through either a O2(1Dg)-mediated photoreaction process or a free radicals mechanism under low oxygen concentration. These results show that molecular dyads, which can form photoinduced charge-separated state, are promising model for phototherapeutic agents with potential applications in cell inactivation by PDT.