New potential cyclohexene-cyanine based photosensitizers for targeting drug delivery systems

Photodynamic therapy (PDT) and antimicrobial photodynamic therapy (APDT) have emerged as the efficient treatment modalities in treatment of cancer and pathogenic bacterial diseases. The main advantage of these medications is their minimal side effects over conventional chemotherapy and antibiotic therapy. PDT utilizes dye molecules (photosensitizers) that generate various cytotoxic species upon light exposure, and these reactive species kill abnormal cells around. The main issues with current photosensitizers are insufficient phototoxicity under the near-infrared (NIR) light irradiation and the lack of targeting specificity to cancer cells and pathogenic bacteria.

To address these issues, we synthesized and investigated novel, NIR-excitable indolenine-, benzothiazole- and benzoselenazole-based cyclohexene-cyanine photosensitizers IR-786, IR-S and IR-3Se, respectively, that can further be linked to cancer-specific and pathogen-specific carriers such as antibodies, peptides, nanoparticles, and bacterial substrates to yield targeting photosensitizing drug delivery systems. These dyes with the absorption maxima at 774 nm, 808 nm, and 813 nm were investigated as photosensitizers for eradication of S.aureus and E.coli pathogenic bacteria. Importantly, upon the NIR light exposure all of these dyes efficiently kill S.aureus at an extremely low concentration of 5 nM. In the next step we intend to employ these new photosensitizers to develop targeting drug delivery systems.