The chemistry, photophysics and photosensitizing properties of phthalocyanines

Phthalocyanines (Pcs) and naphthalocyanines (Ncs) are being extensively studied as photosensitizers for photodynamic therapy (PDT) of cancer. They strongly absorb clinically useful red light, with maxima around 670 nm and 770 nm respectively. Chelated with appropriate diamagnetic metal ions, they exhibit high triplet yields and long triplet lifetimes. Energy transfer from the triplet dye to ground-state oxygen to yield singlet oxygen appears to be the main photosensitizing pathway in biological systems. Underivatized Pcs and Ncs can be incorporated in liposomes for in vivo administration. Sulphonation renders the dyes water soluble but also enhances dimerization to yield photochemically inactive aggregates. Tumour retention and cell membrane penetration of the dyes are strongly affected by the polarity of the macrocycle as well as the nature of the central metal ion and axial ligands. Among the sulphonated dyes, amphiphilic mono- and disulphonated derivatives exhibit particularly good cell membrane-penetrating properties, although the more highly sulphonated dyes show better tumour retention in vivo. At least in vitro, Pc dyes are more photoactive than the corresponding Nc dyes, which probably reflects the lower photostability of the latter.