Cerium halves: nanoparticles will keep cells from being killed by radiation therapy

Scientists have synthesized nanoparticles based on cerium oxide and bioactive molecule that selectively protect healthy cells from death when exposed to X-rays. Thus, nanoparticles support the work of antioxidant systems of normal cells, while in cancer cells, on the contrary, stimulate the production of reactive oxygen species that lead to damage to cellular structures. This effect is likely due to the fact that cancer cells have an acidity different from normal cells. Due to this development, it can be used to reduce the negative effects of radiation therapy in the treatment of cancer.

How cerium oxide nanoparticles work

One of the most common methods of cancer treatment is radiation therapy, in which the tumor is destroyed by X-ray, gamma or other ionizing radiation. It triggers oxidative processes that damage DNA, proteins, membranes and other structures, resulting in cell death. At the same time, radiation therapy acts indiscriminately: along with tumor cells, healthy cells are also killed, which has a bad effect on the state of the body. Therefore, scientists are looking for ways to make radiation therapy to trigger oxidation only in cancer cells.

Scientists from the Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences (Pushchino) and Saratov National Research State University named after N.G. Chernyshevsky synthesized nanoparticles based on cerium oxide - a biocompatible compound capable of engaging in a large number of redox reactions. Cerium oxide can protect healthy cells from damage during radiation therapy, while enhancing DNA damage in cancer cells. The authors decided to increase the selectivity of cerium oxide by attaching to it pyrroloquinolinquinone - a bioactive molecule that has a high antioxidant effect and is involved in the regulation of mitochondria.

The authors precipitated nanoparticles from cerium chloride solution and chemically "hinged" on their surface molecules of pyrroloquinolinquinone. Scientists in different concentrations applied the resulting complexes on healthy cells of connective tissue of the mouse - fibroblasts - as well as on cancer cells. This allowed them to determine the amounts in which nanoparticles do not cause mass death of either cell type. In further experiments with X-rays, the researchers used exactly these concentrations of nanoparticles.

It turned out that X-rays reduced the viability of fibroblasts by 75% and cancer cells by 32%. However, after treatment with nanoparticles and irradiation, the survival rate of healthy fibroblasts increased by 45% compared to control cells, which did not experience any effects, but also died in small numbers due to natural causes. In the case of tumor cells, the survival rate was 31-37% lower than in the control group - this is comparable to the results obtained with irradiation alone without nanoparticles.Thus, nanoparticles practically do not reduce the survival rate of normal cells, but significantly reduce it in cancer cells.

Photo: RIA Novosti/Alexei Sukhorukov

According to the authors of the work, the selective toxic effect in relation to cancer cells is due to the fact that they are acidity of the environment differs from that of healthy cells. Because of this change the properties of nanoparticles, and under the influence of X-rays they do not have the same antioxidant effect.

- The observed effect is due to the fact that cerium oxide nanoparticles modified with pyrroloquinolinquinone reduce the level of reactive oxygen species in fibroblasts and thus save them from oxidation. Because of this, they can be used to keep healthy cells from being killed by radiation therapy for cancer. In the future, we plan to conduct experiments on other types of healthy and cancer cells to better understand how nanoparticles work in each case, - said the project leader, Ph.D. in Biology, leading researcher, head of the laboratory of isotope studies ITEB RAS Nelly Popova.

Theuse of nanoparticles as amplifiers of ionizing radiation in the therapy of oncological diseases, especially in the treatment of inoperable tumors and their metastases, is an extremely promising area that has been actively developing over the past decade, said Andrei Lomonosov, deputy head of the NTI HealthNet working group in the direction of "Biomedicine", scientific consultant of JSC "R-Pharm".

- The project, by reducing the overall radiation load on the patient, may open up the possibility of effective cancer therapy for those patients for whom a high radiation load is contraindicated," he said.

The search for stimulus-sensitive agents for the treatment of oncology is one of the most sought-after research areas. Thenumber of diseases is huge, and the cost of treatment is expensive, said Evgeny Alexandrov, head of the Laboratory of Molecular Modeling of the NTI Competence Center "Digital Materials Science: New Materials and Substances" at Bauman Moscow State Technical University. The situation is complicated by the fact that there are many types of oncology, and for each of them it is necessary to select the optimal treatment.

Photo: RIA Novosti/Alexei Nikolsky

Progress in research occurs every year. Treatment methods practiced a few years ago may no longer be the most effective and affordable this year.

- However, before being used in practice, it is necessary to conduct a full range of necessary research, including on living organisms. Understanding the mechanisms of drug action at the molecular level can significantly accelerate this process. The key should be matched to the lock, not the other way around," he said.

The development is potentially promising, but in order to make final conclusions, it is necessary to conduct additional research, confirmed the expert of the STI Healthnet market, Head of the Oncology Department of SamSMU, Professor Oleg Kaganov.

- If the results of preclinical and clinical studies are positive, the development may have a high potential for implementation," he believes.

The results of the study, supported by a grant from the Russian Science Foundation (RNF), were published in the journal Antioxidants.