Anemone in a package
TPU scientists have more reliably "packed" the actinium isotope into nanocapsules for safer anti-cancer therapy
Scientists of Tomsk Polytechnic University together with colleagues from Russian research centers have proposed an improved version of "nanopackage" for the radioactive isotope actinium-225, used in anti-cancer therapy. Researchers have developed nanocapsules and a new method of "packing" an isotope in them. They are more reliable than analogues to keep anemones inside, minimizing the risks of releasing decay byproducts that are toxic to living cells. The results of the study are published in the journal ACS Applied Materials & Interfaces (Muslimov et al., Calcium Carbonate Core–Shell Particles for Incorporation of 225Ac and Their Application in Local α-Radionuclide Therapy).
The isotope actinium-225 emits alpha particles during decay and is considered an extremely promising radiopharmaceutical for the treatment of various types of oncological diseases, including at the last stage. This is due to the fact that the radius of alpha radiation is smaller than in the case of beta rays, so it "hits" cancer cells more precisely, without hitting healthy ones. But actinium-225 has a serious drawback: when it decays, toxic daughter isotopes are formed – francium-221 and bismuth-213. They accumulate in the liver, kidneys and spleen. This is what hinders the widespread use of actinium in clinical practice.
"The attention of scientists and doctors is focused on actinium also because it is considered a universal isotope, that is, in theory it can be used to treat various types of oncological diseases. But it all comes down to its toxicity. There are two tasks here: to quickly deliver actinium to cancer cells, while simultaneously protecting the patient from alpha decay byproducts. And now there is no fully developed technology in the world that allows this to be done," says Alexander Timin, one of the authors of the article, a leading researcher at the TPU Research School of Chemical and Biomedical Technologies. "The most reasonable approach is considered to be when the isotope is packed into a capsule of a biodegradable polymer, which over time breaks down into harmless elements in the body."
According to the researcher, a physical method is usually used for packaging. The isotope is simply mixed with polymer spheres. So it remains on the surface and partially penetrates into the pores.
"This design is not very reliable. We connected chemistry. First, we bound the isotope to an albumin molecule. Then we placed this pair in a polymer solution, in which albumin formed a strong covalent bond with the polymer, that is, literally surrounded the protein and the isotope with it with a sphere. We used a commercially available polymer based on polypeptides and polysaccharides," says Alexander Timin.
For the experimental part of the study of actinium-225, specialists of the A.I. Leipunsky Institute of Physics and Energy (part of the Rosatom structure) have worked out. The capsules themselves were synthesized by scientists of Tomsk Polytechnic University, they also carried out the "packaging" process.
"The half-life of actinium-225 is ten days, and the capsule remains stable for at least two weeks. This was confirmed by experiments," the scientist explains.
Experiments on laboratory mice were conducted on the basis of the Russian Scientific Center of Radiology and Surgical Technologies named after Academician A.M. Granov in St. Petersburg. The scientists worked with cells affected by melanoma, a skin cancer.
"The study showed that compared to similar systems, when the physical method of communication was used, our capsules allowed to increase the therapeutic effect of actinium by up to 40%. The data "in vitro" showed that the stability of our capsules is 70-80% higher. Animal data demonstrated the accumulation of the drug in the kidneys no more than 5% of the total volume, in similar systems the accumulation was 30-35% and up to 50%. This indicates that the capsule retains by-products reliably enough for potential use in clinical trials. However, the capsules must first pass the preclinical testing stage. We are now looking for a research center to conduct them," adds Alexander Timin.
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