Photophysics of Glycosylated Ring-Fused Chlorin Complexes and Their Photosensitizing Effects on Cancer Cells

The future of photodynamic therapy (PDT) as a promising cancer treatment relies on the development of new selective and effective photosensitizers (PS) with improved photophysical and biochemical qualities. Herein, we present the synthetic procedure, photophysical properties and photosensitizing effects of novel glycosylated 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine] fused chlorin agents featuring either glucose, galactose, or N-acetyl glucosamine. It is shown that both the proto- and Zn2+-ion forms of the ring-stabilized glycochlorins exhibit the required photophysical properties in terms of triplet excited states and singlet oxygen generation, the latter more than 50 % in organic solvents such as CHCl3. Employing the rat AY-27 and human T24 cancer cell models, it was found that these are superior to the corresponding unglycosylated chlorin in biological activity, and moreover, the proto form is 2-3 times superior to the Zn-stabilized variant. Provisional flow cytometry and cell localization studies of the proto-form indicate both necrotic and apoptotic biological activity, and that the photosensitizer localizes in the mitochondria, cell membrane and lysosomes. However, the localization into the lysosomes is dominating and increases substantially with time. We anticipate the findings will aid in the development of photosensitizers for targeted cancer PDT. ; Funding Agencies|Swedish Research Council [2016-00748]; Forte [2016-00748] Funding Source: Forte; Swedish Research Council [2016-00748] Funding Source: Swedish Research Council; Vinnova [2016-00748] Funding Source: Vinnova