Book of Abstracts - Ruhr-Universität Bochum

OP-11
ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
Influence of the Rhenium-Platinum antitumor system on tumor growth and blood
antioxidant state
Nataliia I. Shtemenko, a Alexander V. Shtemenko b
a Department of Biophysics and Biochemistry, Dnipropetrovs’k National University, 72 Gagarin
avenue, Dnipropetrovs’k 49010, Ukraine, b Department of Inorganic Chemistry, Ukrainian State
Chemical Technological University, Gagarin avenue 8, Dnipropetrovs’k 49005, Ukraine. E-mail:
ashtemenko@yahoo.com
The novel antitumor system including cluster rhenium compounds and cisplatin (Re-Pt 4:1 system)
has been recently presented 1 that was effective in the model of rat’s specific Guerink carcinoma T8
and in the majority of experiments led to disappearance of cancer cells. The approach to circumvent
such drawbacks of the drugs on the base of heavy metal compounds as dose-limiting toxicities
(nephro-, hepato-, neurotoxicity, etc.) by encapsulation of the drug into a nanoparticle prevents byside
interactions is a very promising strategy in medicine 2 . Oxidative stress-induced activation of
NADPH oxidase and peroxisome proliferators-activated receptors, alterations of redox state of
binding proteins, DNA mutations and induction of early response genes and hematopoietic activation,
etc. seem to be common elements in the induction of hyperplasia, neoplasia, cancer metastasis, and
angiogenesis. In the present work we show application of different nano-preparations of 20 – 100 nm
size, nanoliposomes and solid nanoparticles loaded with Re-Pt system or with its components in
different ratios in the model of tumor growth. The cluster rhenium compounds dichlorotetra-�isobutiratodirhenium(III)
[Re2(i-C3H7CO2)4Cl2] (Re1) and cis-Re2(C10H15COO)2Cl4·2(CH3)2SO (Re2)
tetrachlorodi-µ-adamantylcarboxylatodirhenium(III) with dimethyl sulfoxide as axial ligands were
the matter of concern. Parameters of oxidative stress in blood of experimental animals were
measured. Intensity of peroxide oxidation process (POL), activity of catalase (C) and superoxide
dismutase (SOD) in plasma and red blood cells were very sensitive to tumor growth and to its
prevention by the system. Introduction of the Re-Pt system in nanoliposomes and nanoparticles did
not influence on the inhibition of tumor growth, except experiments, where quantity of cisplatin in
capsules were lower (1:8). The lowering of the size of the introduced liposomes and particles did not
influence on the intensity of POL: concentration of malonic dialdehyde was not changed. Activities
of SOD and C in plasma and erythrocytes were higher, especially in experiments with solid
nanoparticles (in 1.8 times in comparison with application of ordinary liposomes). This activation of
the antioxidant enzymes was independent from the size of the tumor and remained on the high level
even in those experiments, where ratio of introduced Rhenium compound : cisplatin was 1 : 8. In this
work we show also that influence of rhenium compounds on the enzymes activity is dependent from
the structure of organic radical in the investigated rhenium substance. Encapsulation of the rhenium
substances (first component) into lipid coating is effective as in form of liposomes, as in form of
nanoparticles; the Re-Pt system is effective in the form of nanoliposomes with mixed composition
inside (encapsulation of both components) that opens great opportunities to use medicines with
different properties and in ratio of personal inquire in one preparation. Elaboration of solid
nanoparticles formulations of the Re-Pt requires additional investigations as on this stage of
development of the idea it is clear that only one component of the system may be effectively included
into solid lipid coating. Encapsulation of both components is promising, but requires additional
procedures warranting prevention of the interactions between cisPt and rhenium compounds.
Encapsulation of the Re-Pt antitumor system in nanoparticles and nanoliposomes resulted in active
antyhemolytic properties of the systems and activated the specific antioxidant defence.
References
1. (a) N. Shtemenko, P. Collery, A. Shtemenko. Anticancer Res. 2007, 27, 2487-2492. (b) A.
Shtemenko, P. Collery, N. Shtemenko, K. Domasevitch, et al. Dalton Trans. 2009, 26, 5132 - 5136.
2. (a) C. Medina, M.J Santos-Martinez, A. Radomski. British Journal of Pharmacology, 2007, 150,
552-558. (b) K. N. J. Burger, R.W. H. M. Staffhorst. Nat. Med., 2002, 8, 81-84.
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