Among the organometallic anticancer complexes, dirhenium(III) complexes with a quadruple bond are particularly promising due to their lower toxicities than other heavy metal compounds. Notably, several complexes exhibit remarkable tumor suppression activity, synergistic activity with cisplatin, and reduction of cisplatin toxicity.

To protect dirhenium(III) complexes from degradation and biological environment, to increase their solubility, to deliver to the specific target we created and modified targeted nanosystems based on zirconium phosphate (ZrP) loaded with dirhenium(III) complexes. It was found that the interaction occurs due to the coordination of one or two phosphate groups of adjacent layers in the axial position to the complex, which in some cases is accompanied by a change of structural type. This type of intercalation led to relatively high encapsulation efficiency comparing to analogues (Table 1).

It is shown that the structural type of the dirhenium(III) complex affects the size of nanoparticles. The resulting nanoplatelets had sizes ranging from 64 nm and increased to 300 nm with the appearance of chain structure of intercalated rhenium(III) complexes. Such optimal size (100-150 nm) and the shape of the obtained nanosystems (flat hexagonal nanoparticles) promote good permeability to cancer cells. It was found that the dirhenium (III)  complex was fully released in the environment that simulates the tumor environment. 

The combination of two or more drugs inside carriers is a common strategy in the treatment of many classes of cancer and infectious disease. 

This approach is used to achieve therapeutic synergy or a medicinal effect that is greater than the sum of each drug treatment alone. It had already been shown an efficient co-encapsulation of both dirhenium and platinum-based drugs into liposomes that not only demonstrated the anticancer properties of the Re-Pt antitumor system but also antihemolytic, hepato- and nephro- protecting abilities of the system [3].

The addition of cisplatin caused increases in the interlayer space upon intercalation of the rhenium(III) compound, which indicates cisplatin serves as a preintercalator in the system.  It resulted in increased encapsulation efficiency of dirhenium complexes into ZrP nanoparticles comparing to only dirhenium complexes - loaded ZrP nanoparticles.

Moreover, nanoparticles loaded with Re (III) compound - cisplatin system are more stable in aqueous solution comparing to nanoparticles without cisplatin.

Obtained characteristics of the nanoparticles allowed us to propose new stable formulations with long circulation in the body for following trials in anticancer model experiments.