Liposomes loaded with a dirhenium compound and cisplatin: preparation, properties and improved in vivo anticancer activity

Abstract

Liposomes loaded with the rhenium compound (bis-dimethylsulfoxido-cis-tetrachlorodi-μ-pivalatodirhenium(III) (cis–Re₂((CH₃)₃CCOO)₂Cl₄ċ2DMSO, 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.

• Cancer nanotherapy
• cisplatin
• drug combination
• dirhenium compounds
• lipid vesicles

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. These studies were supported by the Ministry of Education and Science of Ukraine (Grants 0107U000528 and 0111U000111), by Fulbright Research Scholar Grant 2012 (USA), by the COST Action CM1105. We express great thanks to Professors Andreas Holzenburg and Paul Cremer and their research groups, (Texas A&M University, College Station, United States).