pH-dependent spectral properties of HpIX, TPPS2a, mTHPP and mTHPC

Lower extracellular pH in tumors as compared to normal tissues has been pro posed to be a factor contributing to the tumor selective uptake of several photosensitizers. Therefore, the pH dependence of absorption and fluorescen ce spectral properties of four different drugs relevant for photodynamic th erapy (hematoporphyrin IX [HpIX], disulfonated meso-tetraphenylporphine [TP PS2a] meso-tetra(3-hydroxyphenyl)porphine [mTHPP] and meso-tetra(3-hydroxyp henyl)chlorin [mTHPC]) has been examined. Spectral analysis of the dyes dis solved in phosphate buffered saline (PBS) indicates pH-dependent modificati on in the physiologically important region (6.0-8.0) only in the case of Hp IX. This modification is probably related to the protonation of carboxylic groups. Spectral changes of HpIX in PBS observed at acidic pH values <5, as well as those of the rest of the drugs (inflection points of titration cur ves occurred at about 5.1, 3.8 and 2.4 for TPPS2a, mTHPP and mTHPC, respect ively), are likely to be due to the protonation of imino nitrogens. The tum or localizing properties of mTHPP and mTHPC reported in the literature appe ar to be due to factors other than pH-dependent changes in the lipophilicit y of the drugs.