ABSTRACT
Tumorigenic cell lines are more susceptible to [Re6Se8I6]3- 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.
Subject(s)
Central Nervous System Neoplasms/drug therapy , Coordination Complexes/pharmacology , Rhenium/pharmacology , Biological Transport/drug effects , Blood-Brain Barrier/drug effects , Brain/drug effects , Brain/pathology , Cell Line, Tumor , Cell Membrane/drug effects , Cell Membrane Permeability/drug effects , Central Nervous System Neoplasms/metabolism , Central Nervous System Neoplasms/pathology , Humans , Selenium/pharmacology , Tissue Distribution/drug effectsABSTRACT
The cluster Re6Se8I63- has been shown to induce preferential cell death of a hepatic carcinoma cell line, thus becoming a promising anti-cancer drug. Whether this cluster induces acute hemolysis or if it interacts with albumin remains unclear. The effect of acute exposure of human red blood cells to different concentrations of the cluster with and without albumin is described. Red blood cells from healthy donors were isolated, diluted at 1% hematocrit and exposed to the cluster (25-150 µM) at 37 °C, under agitation. Hemolysis and morphology were analyzed at 1 and 24 h. The potential protection of 0.1% albumin was also evaluated. Exposition to therapeutic doses of the cluster did not induce acute hemolysis. Similar results were observed following 24 h of exposition, and albumin slightly reduced hemolysis levels. Furthermore, the cluster induced alteration in the morphology of red blood cells, and this was prevented by albumin. Together, these results indicate that the cluster Re6Se8I63- is not a hemolytic component and induces moderate morphological alterations of red blood cells at high doses, which are prevented by co-incubation with albumin. In conclusion, the cluster Re6Se8I63- could be intravenously administered in animals at therapeutic doses for in vivo studies.
Subject(s)
Antineoplastic Agents/adverse effects , Erythrocytes/drug effects , Hemolysis/drug effects , Rhenium/adverse effects , Selenium Compounds/adverse effects , Antineoplastic Agents/chemistry , Cell Line, Tumor , Erythrocytes/pathology , Humans , Rhenium/chemistry , Selenium Compounds/chemistryABSTRACT
A chiral, cagelike, high-nuclearity lanthanide hydroxide cluster containing 60 Er(III) ions is reported. The cluster core possesses a fascinating sodalite-like structure with 24 vertex-sharing cubane-like [Er(4)(mu(3)-OH)(4)](8+) units. The hexagonal face of the sodalite cage features a templating mu(6)-CO(3)(2-) ion. Magnetic studies revealed weak antiferromagnetic interactions.