Conjugate Systems Using Delocalized Cationic Dyes as a Carrier of Photosensitizers to Mitochondria

摘要

Following Photofrin, the first generation photosensitizer, several second generation photosensitizers have been developed with improved characteristics. More recently, third generation photosensitizers are proposed to achieve higher selectivity toward cancer cells/ tumor tissue. Elevated mitochondrial membrane potential of malignant cells has tested as a tool for preferential uptake of certain photosensitizers to cancer cells. In the same line, we designed new conjugate systems where delocalized cationic moiety delivers a photosensitizer to mitochondria. To prove our concept, two prototype conjugates (TPP-Rh and TPP-AO) were prepared using two cationic dyes (Rhodamine and Acridine Orange) and a photosensitizer (tetraphenylporphyrin, TPP). The two conjugates generated singlet oxygen quite well. Interestingly, the two conjugates showed higher cellular uptake by mover than 8 times than TPP-OH as well as higher phototoxicity. In particular, TPP-Rh showed closer localization pattern to mitochondria than TPP-OH.