Comprehensive study of hexarhenium cluster complex Na4[{Re6Te8}(CN)6] - In terms of a new promising luminescent and X-ray contrast agent.

Octahedral rhenium cluster complexes may have considerable potential as therapeutic and diagnostic drugs due to their luminescent and X-ray contrast properties, as well as their ability to generate singlet oxygen upon photoirradiation. However, their potential biological effects and toxicity in vitro and in vivo are rather far from being understood. Thus, the aim of our research was to study cytotoxicity, intracellular localization and cellular uptake/elimination kinetics in vitro, biodistribution and acute intravenous toxicity in vivo of a complex Na4[{Re6Te8}(CN)6] as the promising compound for biomedical application. The results have demonstrated that the complex penetrates through cell membranes with the maximum accumulation in cells in 24h of incubation and have low toxic effects in vitro and in vivo. The median lethal dose (LD50) of intravenously administrated Na4[{Re6Te8}(CN)6] is equal to 1082±83mg/kg. These findings will be useful for future development of cluster-based agents for different biomedical applications.

Globular chitosan treatment of bovine jugular veins: evidence of anticalcification efficacy in the subcutaneous rat model.

Vascular xenografts are widely used in cardiovascular surgery as an alternative to autologous vessels and vascular allografts. Calcification is one of the main drawbacks of vascular grafts, especially among young patients and children. Among different anticalcification approaches, chitosan emerges as a highly promising candidate due to its versatility, natural origin, and biocompatibility. We investigated the anticalcification efficacy of globular chitosan ("Chitozol") as it demonstrated the improved rate of water solubility as compared with conventional linear macromolecules of chitosan. In addition, we supposed that compact globular form of "Chitozol" molecules could provide effective penetration of extracellular matrix of bovine jugular veins (BJVs). Our results revealed that "Chitozol" treatment mitigated calcification in the experimental groups as compared to the control groups (without any treatment, conventional treatment with glutaraldehyde, and commercially available Contegra conduit). Different concentrations of "Chitozol" (0.3% and 3%), as well as different incubation times (15 and 30min), were equally effective in the prevention of calcification. In addition, "Chitozol" treatment with decellularization of BJVs demonstrated slightly improved stress-strain properties of unimplanted samples. Thus, the filling of fresh BJV with globular chitosan is proposed as a promising emerging treatment for the mitigation of calcific degeneration in BJVs xenografts.

Globular chitosan prolongs the effective duration time and decreases the acute toxicity of botulinum neurotoxin after intramuscular injection in rats.

Botulinum neurotoxin (BoNT) is used for an increasing number of neurological and non-neurological indications and disorders. Since the duration of action of this neurotoxin is limited, the goal of the work was to improve the pharmacological time course of BoNT. We explored the effect of several polysaccharides on the duration of action of BoNT/A1 in rat electromyography. The formulation of BoNT/A1 containing globular chitosan increased the threshold stimulation intensity almost 2 times in 30 days after injection if compared with the baseline threshold. However, conventional linear chitosan, heparin and hyaluronic acid did not have such an effect. In addition, we compared the effectiveness of different doses of BoNT/A1 (25, 50, 75, and 100 U) with globular chitosan and compared the acute toxicity of this formulation with that of BoNT/A1 in physiological saline after intramuscular injection. The results demonstrated that the dose 25 U of BoNT/A1 with globular chitosan was both effective and safe for animals after intramuscular injection. The assessed median lethal dose (LD50) for intramuscular injection in rats was 1.4 times higher for a combination of BoNT/A1 with globular chitosan than that for a solution of BoNT/A1 in physiological saline. Thus, the results of our study have provided evidence that intramuscular injection of the formulation of BoNT/A1 (25 U) containing globular chitosan in rats is safe and significantly prolongs the effective duration time of BoNT/A1.

A comparative study of hydrophilic phosphine hexanuclear rhenium cluster complexes' toxicity.

The octahedral rhenium cluster compound Na2H8[{Re6Se8}(P(C2H4CONH2)(C2H4COO)2)6] has recently emerged as a very promising X-ray contrast agent for biomedical applications. However, the synthesis of this compound is rather challenging due to the difficulty in controlling the hydrolysis of the initial P(C2H4CN)3 ligand during the reaction process. Therefore, in this report we compare the in vitro and in vivo toxicity of Na2H8[{Re6Se8}(P(C2H4CONH2)(C2H4COO)2)6] with those of related compounds featuring the fully hydrolysed form of the phosphine ligand, namely Na2H14[{Re6Q8}(P(C2H4COO)3)6] (Q = S or Se). Our results demonstrate that the cytotoxicity and acute in vivo toxicity of the complex Na2H8[{Re6Se8}(P(C2H4CONH2)(C2H4COO)2)6] solutions were considerably lower than those of compounds with the fully hydrolysed ligand P(C2H4COOH)3. Such behavior can be explained by the higher osmolality of Na2H14[{Re6Q8}(P(C2H4COO)3)6] versus Na2H8[{Re6Se8}(P(C2H4CONH2)(C2H4COO)2)6].

Cellular internalization and morphological analysis after intravenous injection of a highly hydrophilic octahedral rhenium cluster complex - a new promising X-ray contrast agent.

The octahedral cluster compound Na2 H8 [{Re6 Se8 }(P(C2 H4 CONH2 )(C2 H4 COO)2 )6 ] has been shown to be highly radio dense, thus becoming a promising X-ray contrast agent. It was also shown that this compound had low cytotoxic effect in vitro, low acute toxicity in vivo and was eliminated rapidly from the body through the urinary tract. The present contribution describes a more detailed cellular internalization assay and morphological analysis after intravenous injection of this hexarhenium cluster compound at different doses. The median lethal dose (LD50 ) of intravenously administrated compound was calculated (4.67 ± 0.69 g/kg). Results of the study clearly indicated that the cluster complex Hn [{Re6 Se8 }(P(C2 H4 CONH2 )(C2 H4 COO)2 )6 ]n-10 was not internalized into cells in vitro and induced only moderate morphological alterations of kidneys at high doses without any changes in morphology of liver, spleen, duodenum, or heart of mice. Copyright © 2016 John Wiley & Sons, Ltd.

Cellular internalisation, bioimaging and dark and photodynamic cytotoxicity of silica nanoparticles doped by {Mo6I8}4+ metal clusters.

Silica nanoparticles (SNPs) doped by hexanuclear molybdenum cluster complexes [{Mo6X8}L6]n (X = Cl, Br, or I; L = various inorganic or organic ligands) have been recently suggested as materials with high potential for biomedical applications due to both their outstanding photoluminescence properties and their ability to efficiently generate singlet oxygen upon photoirradiation. However, no studies were undertaken so far to prove this concept. Therefore, here we examined the potential of photoluminescent SNPs doped by {Mo6I8}4+ for applications such as bioimaging and photodynamic therapy using the human epidermoid larynx carcinoma (Hep-2) cell line as a model. Our results demonstrated both: (i) significant luminescence from cells with internalised molybdenum cluster-doped SNPs combined with the low cytotoxicity of particles in the darkness and (ii) significant cytotoxicity of the particles upon photoirradiation. Thus, this research provides strong experimental evidence for high potential of molybdenum-cluster-doped materials in biomedical applications such as optical bioimaging, biolabeling and photodynamic therapy.

Prospects of molybdenum and rhenium octahedral cluster complexes as X-ray contrast agents.

Investigation of new X-ray contrast media for radiography is an important field of science since discovering of X-rays in 1895. Despite the wide diversity of available X-ray contrast media the toxicity, especially nephrotoxicity, is still a big problem to be solved. The octahedral metal-cluster complexes of the general formula [{M6Q8}L6] can be considered as quite promising candidates for the role of new radiocontrast media due to the high local concentration of heavy elements, high tuning ability of ligand environment and low toxicity. To exemplify this, the X-ray computed tomography experiments for the first time were carried out on some octahedral cluster complexes of molybdenum and rhenium. Based on the obtained data it was proposed to investigate the toxicological proprieties of cluster complex Na2H8[{Re6Se8}(P(CH2CH2CONH2)(CH2CH2COO)2)6]. Observed low cytotoxic and acute toxic effects along with rapid renal excretion of the cluster complex evidence its perspective as an X-ray contrast media for radiography.