Radiation is used in a wide variety of diagnostic and treatment procedures in medicine. In spite of a great deal of research dedicated to the problem, there is still no widely used drug or material that can provide protection from radiation exposure. Amifostine is a drug that was specifically developed as a radioprotectant. However, the FDA only approved its use to protect salivary glands. Repeated injections are necessary in order for it to be effective. It can pose severe threats to health due to systemic toxicity and complications when it is applied under total body irradiation conditions.
Researchers at the Center for Nanoparticle Research, within the Institute for Basic Science (IBS, South Korea) in collaboration with their colleagues at Seoul National University, School of Dentistry and Dental Research Institute, have reported that they have developed a highly effective and safe nanocrystal which can be used to combat dangerously high doses of radiation. Manganese oxide (Mn3O4) nanocrystals are grown on top of Cerium oxide (CeO2) nanocrystals. This increases their catalytic activity to prevent dangerous side effects of deadly radiation.
Hyeon Taeghwan is the director of the IBS Center for Nanoparticle Research (Seoul National University Distinguished Professor). He says, “Excessive reactive oxygen species (ROS) are found in a number of major diseases including sepsis, cancer, cardiovascular disease, and Parkinson's disease, just to name a few. A powerful antioxidant that can work at low doses only can ensure sustainable applications of radiation in medical, industrial and military settings and more. These new CeO2/Mn3O4 hetero-structured nanocrystals are five times stronger than when CeO2 or Mn3O4 does the job alone.”
When a human body is exposed to high levels of radiation, a huge amount of ROS are generated within milliseconds. This is caused by the decomposition of water molecules. These ROS cause severe cell damage and often lead to death. The research team studied CeO2 and Mn3O4 nanoparticles because they are known for their abilities to scavenge ROS. The problem that had to be solved was exactly how these powerful antioxidant nanomaterials could be used in a safe and economic way. While CeO2 and Mn3O4 nanoparticles are very effective in removing ROS, they can only accomplish this in very high doese. They are also difficult to source rare materials.
The research team employed the approach that is usually taken in work on catalysts. This consists of stacking nanoparticles with different lattice parameters which results in surface strain and increases the oxygen vacancies on the surface of the nanocrystal. Han Sang Ihn is the first author of the study. He explains that “The synergistic effect of the strain generated on Mn3O4 and the increased oxygen vacancy on the CeO2 surface improved the surface binding affinity of the ROS, boosting the catalytic activity of the nanocrystals.” Cho Min Gee is the the co-first author of the study. He says that “Strain engineering of nanocrystals, mainly studied in the field of catalysts, has now been extended to the medical field to protect cells from ROS-related diseases.”
The research team investigated the safety as well as the effectiveness of these new nanocrystals. Molecular dynamics are analyzed by using acute radiation models of human intestinal organoids. Sang-woo Lee says, “Organoids pretreated with the CeO2/Mn3O4 nanocrystals expressed more genes that were related to proliferation and maintenance of intestinal stem cells and fewer cell-death genes, compared with the no-pretreatment group.”
In a study on mice, the CeO2/Mn3O4 nanocrystals significantly increased the survival rate of the mice to sixty seven percent with a very small dose equivalent to 1/360th of an injection dose of Amifostine. The nanocrystals decreased the oxidative stress to internal organs, circulation, and bone marrow cells. There was no significant sign of toxicity,
Park Kyungpyo is a professor at Department of Dentistry, Seoul National University. He says, “To ensure a safe and wide application of a radioprotectant in the clinic, the key is to maintain high catalytic efficacy in low doses. These CeO2/Mn3O4 nanocrystals prove their powerful antioxidant effects to protect our whole body effectively just in small doses.”