Sensitizers for photodynamic therapy
Photodynamic therapy (PDT) is a noninvasive method of treating malignant tumors and age-related macular degeneration, and is particularly promising in the treatment of multidrug-resistant (MDR) tumors. The PDT strategy is based on the preferential localization of certain photosensitizers in tumor tissues upon systemic administration. The sensitizer is then excited with red or near infrared (NIR) light, generating reactive oxygen species (ROS) including singlet oxygen (1O2) and thus irreversibly damaging tumor cells. Current practice of PDT is limited to a few functionalized porphyrins, however these compounds are not considered to be ideal drugs for use in PDT. Among the limitations, the most prominent is the low extinction coefficient of porphyrins in the body’s therapeutic window (650–800 nm, low absorptivity region in typical mammalian tissues). Therefore, there is a significant impetus to develop novel and more efficient sensitizers for use in PDT. Our first contribution[1] to the field was a water soluble perylenediimide derivative with absorption in the red end of the visible spectrum. We have recently disclosed our work in extending the conjugation in BODIPY dyes, resulting in novel dyes with strong absorptions in the red and near IR region of the spectrum. We have then reported BODIPY derivatives which are efficient generators of singlet oxygen, and studied[2] their photocytotoxicity on human leukemia cells (K562). Within the last year, we are trying to utilize single walled carbon nanotubes as delivery agents for the PDT. In addition, our ongoing interest in molecular logic gates and photodynamic reagents apparently converged in one study, yielding the first example[3] of a PDT agent which is at the same time a molecular AND logic gate. This molecular automaton introduces an additional layer of selectivity, generating singlet oxygen at much higher rate only if, both of the selected cancer related cellular parameters are at high levels.
Relevant Publications: [