Liposomes loaded with a dirhenium compound and cisplatin: preparation, properties and improvedin vivoanticancer activity

Abstract

Liposomes loaded with the rhenium compound (bis-dimethylsulfoxido-cis-tetrachlorodi-μ-pivalatodirhenium(III) (cis-Re2((CH3)3CCOO)2Cl4.2DMSO, I) and cisplatin in the molar ratio of 4:1 as well as those loaded only with I were synthesized and characterized by scanning electron microscopy, transmission electron microscopy, dynamic light scattering and electronic absorption spectroscopy. The relative stability of liposomes loaded with I is reflected by a minimal change in the electronic absorption spectra over a period of 8 days whereas the stability of those loaded with both drugs is lower, which we ascribe to the formation of new Re-Pt species inside the liposomes. Furthermore, the investigations of the co-encapsulation effects on the anticancer activity of the Re-Pt system were undertaken. Importantly, the co-encapsulated liposomes exhibit synergistic or additive anticancer activities in vivo, e.g. introduction of these liposomes into tumor-bearing rats demonstrated their antianemic, nephro- and hepato-protecting effects. These liposomes, which are active in cancer treatment, protect the dirhenium compounds from hydrolysis and preserve the biological properties of the Re-Pt hybrid. This study reveals the importance of combined therapy in nanotechnology and medicine.

Rhenium–platinum antitumor systems

“…At the same time the absorption in the area of 20 000 cm -1 (characteristic of dirhenium(III) tetra-μ-carboxylates) decreased. Similar shifts were found in the spectra of other representatives of this structural type -Re 2 (C 3 H 7 COO) 4 Cl 2 , Re 2 (PhCOO) 4 Cl 2 , Re 2 (AdCOO) 4 Cl 2 in their chloroform solution with phosphatidyl choline [35,44,45]. This fact reflected the process of gradual substitution of carboxylic ligands on phosphate groups of phosphatidyl choline around Re 2 6+ -centre.…”

Changes in oxidative stress intensity in blood of tumor-bearing rats following different modes of administration of rhenium-platinum system

“…In our research we studied cluster compound dichlorotetra-μ-isobutyratodirhenium(ІІІ) Re 2 (i-C 3 H 7 COO) 4 Cl 2 -(i) ( 2)] were prepared according to [2].…”

“…All animal experiments were performed in accordan ce with the rules of the European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes (Strasbourg, 1986). Tumor growth was modeled by transplantation of 20% suspension of Guerin's carcinoma cells (T8) in solution to healthy rats (group T8) according to [2]. The compounds of rhenium and platinum were administered by various modes: mode 1 -administration of the compound i alone.…”

“…Such mixed and solid nanoparticles were synthesized and characterized [2]. Administration of the combined Re-Pt system in mixed nanoliposomes and nanoparticles to the experimental animals by the mode 3 was also effective, in terms of both antitumor and antioxidant activities, except for experiments, where the amount of cisplatin within the nanocapsules was increased and where the mixed nanoparticles were administered per os.…”

“…I n our previous work it was shown that cluster rhenium(III) compounds with organic ligands exhibit pronounced anticancer and antiradical activities, particularly in combination with platinum compounds (Re-Pt system) [1,2]. The most studied among them is dichlorotetra-μ-isobutyratodirhenium(ІІІ) Re 2 (i-C 3 H 7 COO) 4 Cl 2 -(I), which both individually and as a part of the Rhenium-Platinum system has anticancer, hepato-and nephroprotective activity.…”