The cluster [Re6Se8I6]3− penetrates biological membranes: drug-like properties for CNS tumor treatment and diagnosis

Abstract

Tumorigenic cell lines are more susceptible to [ReSeI] cluster-induced death than normal cells, becoming a novel candidate for cancer treatment. Still, the feasibility of using this type of molecules in human patients remains unclear and further pharmacokinetics analysis is needed. Using coupled plasma optical emission spectroscopy, we determined the Re-cluster tissue content in injected mice, as a biodistribution measurement. Our results show that the Re-cluster successfully reaches different tissues, accumulating mainly in heart and liver. In order to dissect the mechanism underlying cluster biodistribution, we used three different experimental approaches. First, we evaluate the degree of lipophilicity by determining the octanol/water partition coefficient. The cluster mostly remained in the octanol fraction, with a coefficient of 1.86 ± 0.02, which indicates it could potentially cross cell membranes. Then, we measured the biological membrane penetration through a parallel artificial membrane permeability assays (PAMPA) assay. The Re-cluster crosses the artificial membrane, with a coefficient of 122 nm/s that is considered highly permeable. To evaluate a potential application of the Re-cluster in central nervous system (CNS) tumors, we analyzed the cluster's brain penetration by exposing cultured blood-brain-barrier (BBB) cells to increasing concentrations of the cluster. The Re-cluster effectively penetrates the BBB, reaching nearly 30% of the brain side after 24 h. Thus, our results indicate that the Re-cluster penetrates biological membranes reaching different target organs-most probably due to its lipophilic properties-becoming a promising anti-cancer drug with high potential for CNS cancer's diagnosis and treatment.

Octahedral chalcogenide rhenium cluster complexes with imidazole

“…This includes phosphorescence in the red/near-infrared region upon UV/blue light excitation [1][2][3][4][5][6], electroluminescence [7], their ability to generate singlet oxygen [8][9][10] and high X-ray attenuation efficacy [11][12]. This set of properties opens an avenue to applications such as materials for light emitted diodes [7], photoactive liquid crystals [13][14], optical bioimaging [9][10][15][16], photodynamic therapy [10], imaging agents for X-ray computed tomography [11][12] and others [17][18][19][20][21][22][23]. Notably, by replacing the terminal ligands L, one can both fine-tune the photophysical properties of the octahedral rhenium clusters and target them to a specific application.…”