Two-photon photodynamic therapy.

Abstract

We demonstrate the use of infrared excitation in conjunction with an efficient two-photon absorbing dye and a photosensitizer in photodynamic therapy. An efficient two-photon absorbing dye is excited by short infrared (800 nm) laser pulses, which transfer its energy to the photosensitizer and the photosensitizer, in turn, generates the singlet oxygen. A new approach to photodynamic cancer therapy based on the strong two-photon absorption of certain newly developed organic molecules. Near infrared pulsed laser light efficiently excites these molecules which, in turn, transfer the energy to the photosensitizer used in photodynamic therapy. A newly synthesized two-photon absorbing dye 4-[N-(2-hydroxyethyl)-N-(methyl) amino phenyl]-4'-(6-hydroxyhexyl sulfonyl)stilbene (APSS), which exhibits a strong two-photon absorption at 800 nm, and upconverted fluorescence at 520 nm, in solution in the presence of a photosensitizer was found to generate singlet oxygen under infrared excitation (800 nm). The generation of singlet oxygen in a reaction system containing two-photon absorbing dye and photosensitizer under infrared excitation has been chemically detected by using ADPA (9,10-anthracenedipropionic acid) as singlet oxygen detector. The efficient two-photon absorption of certain chromophores can be used to extend photodynamic therapy to the near infrared spectral region. Whereas the photosensitizer itself may not exhibit two-photon absorption, it could be used in conjunction with one of these new chromophores. The chromophores can act as "photon harvesters" whereby they absorb two photons of near infrared light and transfer the energy to the photosensitizer, which can generate singlet oxygen in the presence of atmospheric oxygen.