Radionuclides in armor
Russian scientists have figured out how to make radiation therapy for cancer safer
RNF Press Service
Radionuclide radiation therapy is one of the most effective methods of treating malignant tumors. With such an impact, the neoplasm is destroyed due to the fact that radionuclides are injected into the patient's blood — unstable atoms that, decaying, emit ionizing radiation. Russian scientists have developed a delivery system that will help minimize the effects of radiation on healthy tissues and protect them from destruction. Results of the research supported by the grant Presidential Program Published in the Journal of Colloid and Interface Science (Karpov et al., Impact of metallic coating on the retention of 225Ac and its daughters within core–shell nanocarriers).
The scheme of the experiment. Figure from the article Karpov et al.
According to According to the International Agency for Research on Cancer (IARC), more than twelve million new cases of cancer and about six million deaths from them are registered annually in the world.
To date, there are three main methods of treating tumors: chemotherapy, surgical removal and radiation therapy. The first two methods are not always effective, because cancer cells eventually acquire resistance to drugs, and all metastases that have spread throughout the body can be impossible to detect and remove. The third method kills tumors flawlessly: it is impossible to acquire resistance to ionizing radiation. During treatment, radionuclides are injected into the patient's bloodstream — unstable atoms whose nuclei disintegrate and form ionizing particles. They carry a large amount of energy that damages tumor cells: destroys their membrane, DNA, changes the biochemical reactions occurring inside them. With the help of special molecular "tags", radionuclides recognize only cancer cells and accumulate at the site of the tumor.
A significant disadvantage of the described approach is that until the radioactive isotope reaches the tumor, it will damage healthy tissues of the body due to the emission of ionizing radiation during radioactive decay. Therefore, scientists are developing special carriers that help to "hold" the radionuclide and its daughter isotopes — the atoms into which it decays — until they are delivered to cancer cells. Peptides (short protein molecules), artificial membrane bubbles, as well as nanoparticles from inorganic compounds are used for this. But the best of them retain a maximum of 84% of radionuclides, and the remaining 16% still affect healthy tissues.
A research group of Russian Scientific Center of Radiology and Surgical Technologies named after Academician A.M. Granov (St. Petersburg), Peter the Great St. Petersburg Polytechnic University (St. Petersburg), ITMO National Research University (St. Petersburg) and the National Research Tomsk Polytechnic University (Tomsk) have developed a system for the delivery of actinium-225 radionuclide (225Ac), which holds more than 98% of these isotopes inside its structure. Scientists have chosen radionuclide 225Ac as a therapeutic agent, since its radioactive decay produces four alpha particles with a large amount of energy sufficient for an effective destructive effect on the tumor. In addition, this isotope, unlike others, has a relatively long half-life, that is, the time during which its activity will decrease by half. The half-life of 225Ac is ten days, which gives an advantage in its production, storage and transportation to medical centers.
As carriers of radionuclide 225Ac, scientists have developed and synthesized nanoparticles consisting of silicon dioxide. Then radionuclides were chemically attached to the nanoparticles and covered with a film of gold or a titanium-containing organic compound on top. It was these additional layers that were supposed to prevent the disconnection of 225Ac from carrier particles and its chaotic circulation through the body, leading to damage to healthy tissues and organs.
To test whether nanoparticles are really capable of retaining radionuclide, biologists injected samples in the form of a suspension into the tail vein of mice. On the first, third and tenth day after therapy, the animals were painlessly killed, and their organs were examined for radioactivity, which was a sign of the decay of 225Ac. As a control group, the researchers used mice injected with pure 225Ac without carrier nanoparticles or with nanoparticles, but without a coating of gold or titanium.
It turned out that in all control variants, on the third day, the radionuclide accumulated in the liver, spleen and lungs, leading to the death of cells of these organs. On the contrary, nanoparticles with 225Ac, additionally coated with a layer of gold or titanium, practically did not harm healthy tissues even after ten days.
"Our development will make it possible to safely deliver radionuclides to tumors without harming healthy tissues of the body. In addition to animal experiments, we conducted in vitro studies — "in vitro" — which proved that the particles synthesized by us keep 225Ac in a stable state for thirty days. The next stage of the study is the modification of the surface of nanoparticles with the help of special molecular "tags" that will allow the components developed by us to migrate to cancer cells, and thereby ensure the selectivity of therapy," says Timofey Karpov, an employee of the nanopharmacology group of the Laboratory of Genetic Engineering of the Russian Scientific Center for Radiology and Surgical Technologies named after Academician A.M. Granov.
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