Systems biology approach for in vivo photodynamic therapy optimization of ruthenium-porphyrin compounds

Two arene ruthenium porphyrin compds. showing interesting photodynamic activity in vitro, [Ru(?6-p-PriC6H4Me)(PMP)Cl2] (PMP = 5-(3-pyridyl)-10,15,20-triphenylporphyrin) and [Ru4(?6-p-PriC6H4Me)4(PTP)Cl8] (PTP = 5,10,15,20-tetra(3-pyridyl)porphyrin) coined Rut1 and Rut4 resp., have been evaluated in vivo. Porphyrins alone and the arene ruthenium porphyrin derivs. (Rut1 and Rut4) showed comparable spectroscopic and photophys. properties. The in vivo study consisted in selecting the optimal arene ruthenium porphyrin photosensitizer by using an original exptl. design approach on mice bearing an ectopic human oral carcinoma xenograft. The model of exptl. design demonstrated to be well suited to the empirical model-building of photodynamic therapy (PDT) response. Arene ruthenium porphyrins concn. and fluence level demonstrated no statistically significant influence on the tumor growth. On the contrary, the presence of ruthenium groups improved the in vivo photodynamic efficiency. By optical fiber fluorimetry, we demonstrated that both compds. exhibited enhanced accumulation in KB tumors from 24 h to 96 h post-i.v. injection. These expts. were completed by inductively coupled plasma mass spectrometry quantification of ruthenium in different organs including tumor tissue. Despite a statistically significant in vivo photodynamic efficiency for Rut4, cellular localization in human oral carcinoma KB cells using fluorescence microscopy demonstrated that both conjugates Rut1 and Rut4 accumulated only in cytoplasm of KB cells but not in the nucleus. [on SciFinder(R)]