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

Paper ID Volume ID Publish Year Pages File Format Full-Text
30657 44495 2012 10 PDF Available
Title
Systems biology approach for in vivo photodynamic therapy optimization of ruthenium-porphyrin compounds
Abstract

Two arene ruthenium porphyrin compounds showing interesting photodynamic activity in vitro, [Ru(η6-p-PriC6H4Me)(PMP)Cl2] (PMP = 5-(3-pyridyl)-10,15,20-triphenylporphyrin) and [Ru4(η6-p-PriC6H4Me)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 24 h 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.

► Experimental design well-suited to the empirical model-building of PDT response. ► The presence of ruthenium groups improved the in vivo photodynamic efficiency. ► Conjugates concentration had no significant influence on the tumor growth. ► Fluence level demonstrated no significant influence on the tumor growth. ► Ruthenium-porphyrin conjugates accumulated only in cytoplasm of KB cells.

Keywords
Combined phototherapy; Ruthenium; Porphyrin; Human oral carcinoma-bearing nude mice; Experimental design approach
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Systems biology approach for in vivo photodynamic therapy optimization of ruthenium-porphyrin compounds
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 117, 5 December 2012, Pages 80–89
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us