Application of Nanoliposomes and Nanoparticles in Rhenium - Platinum Antitumor System

The novel antitumor system including cluster rhenium compounds and cisplatin (Re-Pt 4:1 system) has been recently presented [Anticancer Research, 2007]. The structural types of dirhenium(III) carboxylates with formulas Re2(RCOO)4Cl2, Re2(RCOO)3Cl3, cis-Re2(RCOO)2Cl4, trans-Re2(RCOO)2Cl4, Re2(HPO4)4Cl2, phosphates and mixed carboxylates – phosphates were the matter of concern. The binuclear cluster Re2fragment is a part of these compounds and includes quadrupol rhenium – rhenium bond with δ-component, which plays the role of free radical "scavenger". Introduction of single doses of cisplatin and liposome forms of a rhenium compound according to the scheme of antioxidant therapy have been tested in the model of rat’s specific Guerink (T8) carcinoma. Application of rhenium compounds as biochemical modulators of cisplatin mechanism of action was especially successful and in the majority of experiments led to disappearance of cancer cells. Intensity of peroxide oxidation process (POL), activity of catalase (C) and superoxidedismutase (SOD) in plasma and red blood cells were very sensitive to tumor growth and to its prevention by the system. In the present work we show application of different nano-preparations – nanoliposomes and nanoparticles containing a rhenium compound or Re-Pt system 1:4, 1:8 in the model of tumor growth and compare the results obtained with previous data, where rhenium compounds were introduced as ordinary liposomes and cisplatin in solution. 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 capsulations 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 experiments with 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 8 : 1, nevertheless cisplatin is known as a mighty inhibitor of C and SOD in plasma and red blood cells. 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. The clinical use of drugs on the base of heavy metal compounds usually faces a number of serious problems. Due to its reactive nature, most of the drug is rapidly inactivated by binding to proteins upon entry in the blood by intravenous administration and never reaches the tumor in an active form. Moreover, binding to proteins is considered a major cause of much dose-limiting toxicity exhibited by some citostatics such as nephro-, hepato-, and neurotoxicity. Thus, the approach to circumvent these drawbacks by encapsulation of the drug into a nanoparticle, especially with mixed composition inside, prevents by-side interactions, leads to enhancement of the enzymatic protective system and is very promising strategy in medicine.