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Employees of the Departments of Radiochemistry and High-Molecular Compounds of the Faculty of Chemistry of Moscow State University with colleagues from the V.N. Orekhovich Research Institute of Biomedical Chemistry investigated the antitumor activity of complexes of biocompatible microgel polysaccharide carboxymethylcellulose crosslinked with copper radionuclides. The cytotoxicity of such complexes in relation to cancer cells significantly exceeds the toxicity to healthy tissues. According to the authors, carboxymethylcellulose can become a promising carrier for medicines.

The search for new promising carriers for medicines is one of the most difficult tasks, the solution of which is necessary for modern medicine. Simply injected into the body, the medicine often does not fall into a specific place, but diverges throughout the body. The same applies to radionuclides that are actively used in nuclear medicine. Although they tend to concentrate in certain organs to a greater extent than drugs, a significant part of drugs without special delivery will spread through the body and increase the dose load.

"To solve this problem, many carrier options are offered: nanoparticles, polymers, liposomes and others," said Marina Orlova, a leading researcher at the Department of Radiochemistry, Doctor of Chemical Sciences. – The choice is large, but each option has its drawbacks. The best are considered to be special antibodies called monoclonal. They clearly move to a certain cell and can bring a radionuclide or even a medicine with them. But here there is a difficulty, which consists in the emission of ionizing radiation by radionuclides, which can change the monoclonal antibody itself. We do not know how fast this process is going, but it is known that such damage can deprive a monoclonal antibody of the ability to selectively deliver. There are also difficulties with the delivery of medicines, since the process of attaching the drug itself changes the conformation of the antibody, and, therefore, its properties, which in each case requires additional research and technological solutions."

For nuclear medicine, carriers are needed that do not release radionuclide or "lose" it slightly even with high radiation exposure. Among the components used to create carriers, one of the most promising is the polysaccharide carboxymethylcellulose, which is characterized by solubility in water, low toxicity and high biocompatibility. In addition, carboxymethylcellulose contains a large number of functional groups capable of firmly binding polyvalent metal ions. For example, it can form complexes with copper, two radionuclides of which are actively used in nuclear medicine.

"The complex of carboxymethyl cellulose with copper is a water–soluble microgel. Crosslinking of organic molecules with metal ions reduces the size of microgel particles, which is a positive factor," explained Marina Orlova. – We were particularly interested in how such a microgel would be distributed throughout the body and how it would be excreted, since there is no enzyme in our body that would process cellulose. It turned out that microgels cross-linked with copper are excreted much better than pure carboxymethylcellulose. If you attach a deliverer to such a carrier – a biodegradable vector that can lead it to the right cells – then the radioactive element will not spread throughout the body, which is very good, and after the short-lived radionuclide finishes its work, the polymer will be able to leave the body. An additional bonus of such a microgel is the ability to bind an antitumor drug to it simultaneously with radionuclide, if there is a solid tumor or a radioprotector to protect healthy tissues."

Testing of the complexes was the first stage in the development of a drug for targeted medicine. Next, it is necessary to bind to the carrier, which will lead this complex exactly to the goal.

"Our dream is to make a multifunctional system," Marina Orlova shared. "There are already developments in this area, but the main work is still ahead."

The article was published in the journal Colloids and Surfaces A: Physicochemical and Engineering Aspects
PHOTO: Schematic image of the carrier © MSU Press Service

Source: msu.ru, sci-dig.ru