Photodynamic Therapy | Frontier Specialty Chemicals

PDT is a binary cancer therapy, which relies on selective uptake of a photosensitizer into the cancer cells which upon irradiation with light of an appropriate wavelength produce highly toxic singlet oxygen and other cytotoxic species.^1,2 Singlet oxygen can readily react with electron rich biomolecules such as unsaturated lipids, amino acids and DNA. Ultimately, these destructive reactions lead to cell death through apoptosis or necrosis.³

The following attributes of the porphyrin derivatives make them powerful and versatile chromophores for PDT studies:

1) The presence of main absorption bands in the therapeutic window, the Q bands, around 600-700 nm. It is advantageous to use red-shifted chromophores in order to get better penetration of exciting laser source;

2) Intense extinction coefficients. Singlet oxygen production depends on the extinction coefficient of the chromophore; and

3) Ease of modification of substituent groups. Porphyrins have several distinct functionalization sites, i.e., the meso position, β-position. The solubility of porphyrin derivatives in nonpolar or polar solvents can be modified by varying the porphyrin substituents.

These properties of porphyrin-based photosensitizers allow for deeper photodamage of tissue and a better therapeutic effect compared with non-porphyrinoids.

To overcome the major drawbacks in porphyrin based photosensitizers, low excitation coefficient in the therapeutic window and persistence in skin, so called second generation chlorin based photosensitizers, such as Foscan (Temoporfin), Talaporfin (LS11, N-aspartylchlorin e₆) and HPPH (2-(1-hexyloxyethyl)-2-devinyl-pyropheophorbide a) have been developed.⁴ Chlorins are particularly promising photosensitizers for PDT because of their distinctive ability to accumulate in tumorous tissues,⁵ intense absorptions at 664 nm, high stability, low dark toxicity and ability to generate singlet oxygen in the light.^6,7,8 Amphiphilicity, another favorable trait, has been shown to improve the effectiveness of photosentizers. Ce6 a derivative of chlorophyll a, possess three carboxylic side chains, making it an ideal substrate for synthesis of novel amphiphilic photosensitizers.