Systems biology approach for in vivo photodynamic therapy optimization of ruthenium-porphyrin compounds.
Fiche publication
Date publication
décembre 2012
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BARBERI-HEYOB Muriel, Pr BASTOGNE Thierry
Tous les auteurs :
Pernot M, Bastogne T, Barry NP, Therrien B, Koellensperger G, Hann S, Reshetov V, Barberi-Heyob M
Lien Pubmed
Résumé
Two arene ruthenium porphyrin compounds showing interesting photodynamic activity in vitro, [Ru(eta(6)-p-Pr(i)C(6)H(4)Me)(PMP)Cl(2)] (PMP=5-(3-pyridyl)-10,15,20-triphenylporphyrin) and [Ru(4)(eta(6)-p-Pr(i)C(6)H(4)Me)(4)(PTP)Cl8] (PTP=5,10,15,20-tetra(3-pyridyl)porphyrin) coined Rut1 and Rut4 respectively, have been evaluated in vivo. Porphyrins alone and the arene ruthenium porphyrin derivatives (Rut1 and Rut4) showed comparable spectroscopic and photophysical properties. The in vivo study consisted in selecting the optimal arene ruthenium porphyrin photosensitizer by using an original experimental design approach on mice bearing an ectopic human oral carcinoma xenograft. The model of experimental design demonstrated to be well suited to the empirical model-building of photodynamic therapy (PDT) response. Arene ruthenium porphyrins concentration 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 compounds exhibited enhanced accumulation in KB tumors from 24h to 96 h post-intravenous injection. These experiments 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.
Référence
J Photochem Photobiol B. 2012 Dec 5;117:80-9