Novosibirsk Researchers Pioneering Cancer Therapy Using Molybdenum Clusters

A team of researchers from the Nikolaev Institute of Inorganic Chemistry SB RAS, the Laboratory of polynuclear coordination compounds at Novosibirsk State University and a number of other research institutes of SB RAS and RAMS obtained breakthrough results in proving the efficiency of using molybdenum clusters in cancer therapy. The investigators are conducting extensive pre-clinical studies.

 Morphological changes of cancer cells after incubation with a molybdenum cluster

Chemists from Novosibirsk teamed with biologists to study the influence of molybdenum cluster-doped silica nanoparticles on larynx carcinoma cell lines and were first to prove their efficacy while applying photodynamic therapy to human epidermoid larynx carcinoma. The results were reported in their article Cellular internalisation, bioimaging and dark and photodynamic cytotoxicity of silica nanoparticles doped by {Mo6I8}4+ metal clusters in Journal of Materials Chemistry B.

Apart from Novosibirsk researchers from NSU, NIIC, the Scientific Institute of Clinical and Experimental Lymphology, the Institute of Molecular Biology and Biophysics and the Scientific Research Institute of Physiology and Basic Medicine, the team of 12 Russian scientists included a researcher working now at the Department of Chemistry in the University of Hull (UK).

To physicists and chemists, a cluster means a group of atoms or molecules formed by interactions ranging from very weak van der Waals contacts to strong ionic bonds. Structurally, clusters are intermediate between a molecule and a bulk solid. Metal clusters include metal atoms and can include ligands (ions or molecules that bind to the central metal atom to form a coordination complex). The distance between the ligands being as small as 0.3nm, direct metal-metal bonds become possible

Representation of the molybdenum cluster complexRepresentation of the molybdenum cluster complex

Michael A. Shestopalov, a senior researcher at the Laboratory of polynuclear coordination compounds (Novosibirsk State University) and the Laboratory of synthesis of cluster compounds and materials (Nikolaev Institute of Inorganic Chemistry SB RAS), explains that Novosibirsk researchers have been studying molybdenum and tungsten clusters for quite a while and have discovered a number of features attractive for biomedical applications.

“When exposed to ultraviolet irradiation, molybdenum clusters show significant photoluminescence in the red region. In the presence of oxygen, which is all around us in its triplet non-excited state, the clusters make it turn into an active singlet form,” says Michael.

Singlet oxygen is used in medicine for photodynamic cancer therapy based on applying photosensitisers and laser irradiation at the wavelength corresponding to the photosensitisers’ peak absorption. Novosibirsk researchers decided to create a new photosensitizer based on molybdenum clusters.

Michael Shestopalov stresses that most common photosensitisers such as porphyrins (a group of heterocyclic macrocycle organic compounds containing the parent chemical compound of porphin) have some disadvantages. Their organic compounds are hardly detectable in the organism but for their luminescence.

As molybdenum clusters are metal in their base, they can be used as contrast agents in transmission electron microscopy and X-Ray imaging. It means that the substance can be easily X-Rayed in the organism, which is followed by therapy.

The next step was to modify hexanuclear molybdenum cluster complexes so that they became biocompatible. The complexes were encapsulated within an inert biocompatible carrier matrix, namely SiO2.

Michael explains that SiO2 was not a random choice. It can be easily modified to make nanoparticles as little as 50 nm and internalized into Hep-2 cells, which become abundant with some types of cancer cells. After the conjugation with the antibody, the nanoparticles head for the malignant tumor.

 Effect of the molybdenum cluster on cancer cells before(top) and after (bottom) photoirradiation

The researchers chose a targeted drug Herceptin as the antibody to the HER2 gene as normal cells are not characterized by HER2 hyperexpression and do not accumulate the antibody, while cancer cells demonstrate increased accumulation.

Having studied different cluster complexes with particles of various size, the researchers found an optimal combination which demonstrated good luminescence and relatively good efficiency of singlet oxygen generation. Then they teamed with biologists and were satisfied to see that nanoparticles reached the larynx carcinoma and killed the tumor cells under the influence of the singlet oxygen induced by ultraviolet irradiation.

Michael Shestopalov points out that a medication based on nanoparticles doped by photoluminescent molybdenum clusters is currently undergoing preclinical studies (in-vivo tests).

Prepared by Anastasiya Anikina