SIMULTANEOUS 2-PHOTON ACTIVATION OF TYPE-I PHOTODYNAMIC THERAPY AGENTS

The excitation and emission properties of several psoralen derivatives are compared using conventional single-photon excitation and simultan eous two-photon excitation (TPE), Two-photon excitation is effected us ing the output of a mode-locked titanium:sapphire laser, the near infr ared output of which is used to promote nonresonant TPE directly. Spec ifically, the excitation spectra and excited-state properties of 8-met hoxypsoralen and 4'-aminomethyl-4,5,8-trimethylpsoralen are shown to b e equivalent using both modes of excitation. Further, in vitro feasibi lity of two-photon photodynamic therapy (PDT) is demonstrated using Sa lmonella typhimurium. Two-photon excitation may be beneficial in the p ractice of PDT because it would allow replacement of visible or UV exc itation light with highly penetrating, nondamaging near infrared light and could provide a means for improving localization of therapy, Comp arison of possible laser excitation sources for PDT reveals the titani um: sapphire laser to be exceptionally well suited for nonlinear excit ation of PDT agents in biological systems due to its extremely short p ulse width and high repetition rate that together provide efficient PD T activation and greatly reduced potential for biological damage.