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Etude des interactions du photosensibilisant méta-tétra(hydroxyphényl)chlorine avec les protéines de plasma et les cellules

Abstract : The investigation of the influence of mTHPC distribution in tumor, plasma and leukocytes on PDT response shows that photosensitizer accumulation in leukocytes exhibits a good correlation with PDT efficacy. This result suggests that leukocytes could play an important role in the mechanism of PDT-induced vascular damage.The study of mTHPC monomerisation in the course of interactions with plasma proteins demonstrates slow rate of disaggregation kinetics. The fraction of aggregated mTHPC at equilibrium and sensitizer disaggregation rates strongly depends on protein content and incubation temperature. The data obtained show that in aqueous media mTHPC forms free large-scale aggregates with strong interaction between sensitizer molecules. Kinetic analysis demonstrates that mTHPC is characterized by very slow redistribution rates from the complexes with plasma proteins. Low redistribution rates as compared to other sensitizers are consistent with the unique binding properties of mTHPC. The existence of both collisional and aqueous mediated transfer of mTHPC was supposed. Confocal microscopy study reveals diffuse mTHPC localization pattern at 3h and formation of highly fluorescent spots of sensitizer at 24h incubation in MCF-7 cells. The parameters of sensitizer absorption, fluorescence lifetime and photobleaching have shown that at 24h incubation mTHPC is much more aggregated compared to 3h. The yield of cellular photoinactivation is about 2 times higher for 3h time point. Such difference is attributed to different sensitizer aggregation states and interactions with cellular components. Theoretical and spectroscopic study of mTHPC, mTHPP and mTHPBC allowed us to define their aggregates structure in aqueous media. For this purpose new quantum mechanic semi-empirical method was developed on the basis of which the spectral shifts in different solvents were calculated. mTHPC and mTHPP form linear dimers in aqueous media, whereas mTHPBC form zigzag dimers.
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http://docnum.univ-lorraine.fr/prive/SCD_T_2006_0247_SASNOUSKI.pdf
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https://hal.univ-lorraine.fr/tel-01747002
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Submitted on : Thursday, March 29, 2018 - 10:49:19 AM
Last modification on : Thursday, May 28, 2020 - 10:25:04 AM

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  • HAL Id : tel-01747002, version 1

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Siarhei Sasnouski. Etude des interactions du photosensibilisant méta-tétra(hydroxyphényl)chlorine avec les protéines de plasma et les cellules. Biotechnologies. Université Henri Poincaré - Nancy 1, 2006. Français. ⟨NNT : 2006NAN10247⟩. ⟨tel-01747002⟩

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