Two-photon absorption cross section of excited phthalocyanines by a femtosecond Ti-sapphire laser

In the past few years, photodynamic therapy (PDT) has become a major treatment for neovascular age-related macular degeneration (AMD) in which there is abnormal growth of choroidal neovasculature (CNV) that eventually obscures central vision, leading to blindness. However, one of the main limitations of current PDT is the relatively low specificity of the photosensitizer (PS) and light for pathological tissue which may induce damage to adjacent healthy tissue. An alternative approach to circumvent the specificity limitation is to improve the irradiation process. In particular two photon (2-gamma) excitation promises a more precise illumination of the target tissue. PS are activated by the simultaneous absorption of 2-gamma delivered by ultra-fast pulses of near infrared light. In order to evaluate the efficiency of phthalocyanine (Pc) dyes for 2-gamma absorption we measured 2-gamma absorption cross sections (sigma(2)) of a number of metalated Pc (MPc) dyes at lambda(ex) = 800 nm using a femtosecond laser. The studied Pc molecules vary by the type of the central metal ion (Al or Zn) and the number of peripheral sulfo substituents (MPcS). Each MPc dye of our series shows an improved 2-gamma absorption sigma(2) as compared to that obtained for Photofrin (3.1 +/- 0.1 GM, with 1 GM = 10(-50) cm(4) s photon(-1) mol(-1)), the PS currently approved for 1-gamma PDT. Our data show an 2.5-fold enhancement for AlPcCl, AlPcS2adj and ZnPcS3C9, up to 10-fold (28.6 +/- 0.72 GM) for the ZnPcS4 dye relative to Photofrin. These findings confirm the efficiency of Pc for 2-gamma absorption processes and represent the first detailed comparison study of 2-gamma absorption sigma(2) between Photofrin and Pc dyes.