Structural and physico-chemical determinants of the interactions of macrocyclic photosensitizers with cells.

New therapies have been developed using reactive oxygen species produced by light-activation of photosensitizers (PS). Since the lifetime of these species is extremely short and their diffusion in space is limited, the photo-induced reactions primarily affect the cell organelles labeled by the PS. In addition to the development of molecules with the best optical and photosensitizing properties, considerable research has been done to understand the physico-chemical parameters governing their subcellular localization. In this review, we examine these parameters to establish the structure/efficacy relationships, which allow specific targeting of PS. We examine the effect of subcellular localization on the cellular response to photosensitization processes. We discuss the determinants of subcellular localization, including the hydrophobic/hydrophilic balance, the specific charge effects and the dynamics of PS' transfer through membranes. Specific targeting can also be achieved with molecular structures able to recognize cellular or intracellular receptors, and this is also dealt with in this paper.