Development of nanoparticles that removes the reactive oxygen caused by diagonal radiation exposure
- Minimized side effects by administering low doses… Expected to be used in wide ranges as radiation protection agents-
- Joint research by IBS-Seoul National University, selected for the cover of the international academic journal Advanced Materials-
A protective agent that can protect the whole body from high-dose radiation has been developed.
Professor Kyungpyo Park from SNUSD collaborated with Professor Taeghwan Hyeon of the
IBS Project Group and developed nanocrystal that can remove excess reactive oxygen species (ROS)
caused by irradiation with low doses. The result of the study was released online in a prestigious
international journal called the 'Advanced Materials (IF 27.398)' and it will be published as a
cover article in the August issue. Professor Kyungpyo Park and his advisee doctoral student
Mr. Sang-woo Lee participated in the research as lead authors.
As the use of radiation in medical fields such as diagnostics and anti-cancer treatments has increased,
development of drugs to reduce side effects from radiation exposure has been actively underway worldwide.
When human body is exposed to high levels of radiation, a massive amount of ROS are generated
within milliseconds (ms‧1000th of a second) due to the decomposition of water molecules.
Excessive reactive oxygen species causes damage to cells and in severe cases can lead to death.
Therefore, the fundamental method to protect the human body from radiation is through
minimizing damage to stem cells by rapidly removing excess ROS generated by radiolysis.
Amifostine is currently the only radioprotectant approved by the U.S. Food and Drug Administration (FDA),
but it is only limited to prevent damage to the salivary glands, not the whole body.
Moreover, it may cause side effects due to toxicity. In addition, the effect of the drug is only
significant when administered at a high concentration. Even when it was administered
in high dosage, the effect was decomposed within 30 minutes limiting its use.
To overcome these limitations, the researchers began studying protective agent that reduces
side effects while protecting the whole body from radiation. The researchers first paid
close attention to nanoparticles capable of removing ROS. Cerium oxide (CeO2) and manganese oxide (Mn3O4)
have been known to be effective in reactive oxygen species -related diseases such as septicaemia,
Parkinson's disease, and Alzheimer's. However, when applied at high level to be used as radioprotectant,
it may cause toxicity in the body. Thus, minimizing the dosage was the key solution.
The researchers resolved this problem by improving the ability to remove ROS by controlling
the structure of the nanoparticles. They developed nanocrystals by growing manganese oxide (Mn3O4) nanocrystals
on top of the Cerium oxide (CeO2) nanocrystals. Due to the difference in lattice parameters between
the two nanoparticles, it resulted in synergistic effect of the strain generated on Mn3O4.
Thus increasing oxygen vacancy on the CeO2 surface and improving the surface binding affinity of the ROS.
This new CeO2/Mn3O4 hetero-structured nanocrystals have up shown up to 5 times
higher antioxidant performance than CeO2 or Mn3O4.
The research team checked the safety, as well as effectiveness of this new antioxidant nanocrystals
using acute radiation model of human intestinal organoids. The side effects caused by radiation
such as DNA damage, apoptosis, and stress were dramatically improved by the administration
of nanocrystals, additionally the expression of genes related to cell regeneration increased.
Animal experiments have proven that the protective effect is high even with low doses of nanocrystals.
In a mouse study, the CeO2/Mn3O4 nanocrystals significantly increased the survival rate of the animals
that were exposed to high-dose radiation with a fatality rate of 100% to 67% with only very small dose
(1/360 of Amifostine injection dose). This survival rate is about 3.3 times higher than that of amifostine.
Additionally, it was also found to decrease the oxidative stress to internal organs, circulation, and
bone marrow cells, without any significant signs of toxicity.
Professor Kyungpyo Park stated, “We focused on maintaining high catalytic efficacy in low doses
to ensure a safe and wide application of a radioprotectant in the clinic. The newly developed nanocrystals
have been shown outstanding ROS scavenging abilities while minimizing stem cell damage in various parts
of organs within the body that have been exposed to radiation. The result of our research is expected
to be widely used not only in future cancer patients, but also in nuclear-related industries where
there is always a risk of radiation exposure.”
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