Abstract 497: Mitochondria-targeting photosensitizers activable by two-photon absorption

Abstract

Abstract Two-photon absorption (TPA) is a non-linear optical process, used to activate photosensitizers in the NIR region (700 - 850 nm) thus affording greater tissue penetration in photodynamic therapy (PDT). Since the efficiency of this process has a quadratic dependence on the light intensity, the photodynamic effects are restricted to a small area around the laser's focal point, thus providing spatial selectivity. Although most clinically approved photosensitizers can be activated by TPA, they generally have very small cross-sections (generally below 10 GM around 800 nm). Thus, light intensities required to activate them could damage normal surrounding tissues. The TPA of photosensitizers can however be improved, without perturbing their ability to generate singlet oxygen, by conjugating them to effective TPA chromophores. These then serve as TPA antennae and upon activation transfer their energy to the photosensitizer which then generates singlet oxygen for PDT. In this study a porphyrin-rhodamine B dyad (TPP-Rh), previously demonstrated to target mitochondria, was evaluated as a two-photon photosensitizer for PDT. TPP-Rh, was synthesized by conjugating a monohydroxy porphyrin photosensitizer (TPP-OH) to rhodamine B (Rh B), an effective TPA chromophore, via a saturated hydrocarbon linker, thus enhancing intramolecular FRET between the dyad components and ultimately the photosensitizer's TPA. To evaluate the efficiency of TPP-Rh as a two-photon photosensitizer we studied both its one and two-photon absorption photophysical properties in comparison to those of its individual components: Rh B and TPP-OH. These included: FRET kinetics, FRET dynamics, and the singlet oxygen generation kinetics. A FRET rate of 1.679 × 1012 s−1 and a 99 % FRET efficiency was calculated for TPP-Rh from its spectral properties suggesting efficient FRET from the TPA moiety (Rh B) to the photosensitizer moiety (TPP). In addition to this, TPP-Rh produced singlet oxygen at comparable rates when excited with both TPA at 800 nm and one photon absorption (OPA) at 650 nm. Thus, this indicates that conjugating photosensitizers to rhodamine B could provide several advantages in PDT: deeper tissue penetration, spatial selectivity and selective photosensitizer accumulation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 497.