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Gamaleia N.F.,R.E. Kavetsky Institute of Experimental Pathology | Shishko E.D.,R.E. Kavetsky Institute of Experimental Pathology | Dolinsky G.A.,R.E. Kavetsky Institute of Experimental Pathology | Shcherbakov A.B.,Research Institute for Nanotechnological Industry | And 2 more authors.
Experimental Oncology | Year: 2010

Aim: To synthesize a conjugate of hematoporphyrin with gold nanoparticles, and to evaluate its photodynamic activity in experiments on cultures of transformed cells. Methods: nanosized gold particles and nanocomposites synthesis methods, cell culture methods, photobiology methods, trypan blue dye exclusion test, chemiluminescence assay. Results: Various hematoporphyrin-gold nanocomposites were obtained, which contained similar hematoporphyrin concentration (5 μg/ml) and varied concentrations (0.5-5 μg/ml) of gold nanoparticles with a diameter of 15 nm or 45 nm. It was established by chemiluminescence method that nanocomposites synthesized induce more efficiently the formation of photo-oxidative products than original photosensitizer. The experiments with transformed cell lines showed that photodynamic in vitro activity of synthesized hematoporphyrin-nanogold composites is much higher than that of the original photosensitizer. The better activity of the nanocomposites with gold particles of 45 nm vs such of 15 nm which was demonstrated in the experiments, can be apparently connected with the fact that bigger particles are able to transport more porphyrin molecules into malignant cells. Conclusion: The results obtained warrant the necessity of further studies with hematoporphyrin-gold nanocomposites in vivo on transplanted tumors of animals which have to define the real perspectives of the nanocomposites application in PDT. Copyright © Experimental Oncology, 2010.

Gamaleia N.,R.E. Kavetsky Institute of Experimental Pathology | Dolinsky G.,R.E. Kavetsky Institute of Experimental Pathology | Shishko E.,R.E. Kavetsky Institute of Experimental Pathology | Shcherbakov A.,Research Institute for Nanotechnological Industry | And 3 more authors.
Forum on Immunopathological Diseases and Therapeutics | Year: 2011

Photodynamic therapy (PDT) is a modern, selective, and noninvasive method of treating tumors, but its practical application is limited by poor penetration of light into biological tissues. Photosensitizers, combined with nanoparticles serving as a transportation vector, accumulate better in tumor tissues and make them more light responsive, even to scarce light penetration. We prepared a combined photosensitizer from Fotolon (chlorin e6) doped with gold nanoparticles (GNP). The GNP-doped Fotolon showed higher photodynamic activity for MT-4 cell line than Fotolon alone. Because singlet oxygen ( 1O 2) and free radicals are considered to be the main effectors of PDT, we attempted to evaluate a role of these oxidative factors in photodynamic effects of Fotolon in comparison with its GNP-doped analog. 1O 2 trapping by sodium azide reduced the increase in cell death, caused by GNP doping. Nevertheless, fluorescence assay with an 1O2-specific sensor revealed a decrease in 1O 2production by GNP-doped Fotolon. To resolve the contradiction, further investigation of intrinsic Fotolon fluorescence and free radical oxidation-derived chemiluminescence in phospholipid model system were performed. Our results support the primacy of the PDT type II mechanism with a subsequent increase in secondary free-radical generation through GNP catalytic activity. © 2011 by Begell House, Inc.

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