Photodynamic therapy (PDT) is a proven clinical tool for the treatment of cancer. The principle behind PDT is that the in-vivo dye absorbs near-IR light and by energy transfer forms highly reactive singlet oxygen, which destroys the tumour cell. Many groups have studied various compounds for PDT, among them halogenated squaraines. These are promising singlet oxygen producers in organic solvents, but squaraines form non-fluorescent aggregates in water and they also decompose during the PDT process.

For clinical use, the photosensitizing dye should rapidly disappear after PDT, otherwise phototoxicity becomes a problem. However, in the research lab, highly stable photosensitisers are needed for systematic studies of the effects of reactive oxygen species on cells and tissue. 

Bradley Smith and colleagues at the University of Notre Dame has discovered that both aggregate formation and decomposition are eliminated when a squaraine is encapsulated inside a protective macrocycle to form a squaraine-rotaxane couple. They have found that an iodinated homologue is an excellent photosensitiser for singlet oxygen in aqueous solution yet the dye is not destroyed by the singlet oxygen. Smith expects these highly stable, halogenated squaraine-rotaxanes to be useful research tools to create reactive oxygen species in a clean and controlled manner. More generally, this work suggests that encapsulation of a chromophore in a rotaxane may be a general way to circumvent the decomposition encountered with many dyes explained Smith. 

According to Smith, their immediate goal is to conduct biological studies to evaluate the ability of these squaraine-rotaxanes to kill cells by PDT. They also plan to study next-generation squaraine-rotaxanes with larger numbers of halogen substituents to increase the yield of singlet oxygen. 

For longer-term studies Smith notes that 'A major challenge is to develop targeting strategies that ensure selective delivery of the dyes to specific cells or tumours. One approach is to attach tumour-targeting ligands to the squaraine-rotaxanes. An advantage with squaraine-rotaxanes is that chemical conjugation is comparatively easy since the dyes are extremely stable, even under vigorous reaction conditions.'