Key decay mechanism behind superior biological effects of heavy-ion cancer therapy uncovered

Heavy-ion therapy, one of the most advanced radiotherapy techniques, has proven to be more effective than conventional X-rays and proton radiation in cancer treatment. However, the mechanisms behind this superior biological effectiveness remain unclear.

Published in Physical Review X on March 11, a new study has uncovered a key mechanism involving intermolecular Coulombic decay (ICD) in aqueous environments initiated by heavy-ion irradiation, providing insights about the effectiveness of such irradiation.

The study was conducted by researchers from the Institute of Modern Physics (IMP) of the Chinese Academy of Sciences (CAS), in collaboration with researchers from Russia’s Irkutsk State University, Germany’s Heidelberg University, the University of Science and Technology of China, Xi’an Jiaotong University, and Lanzhou University.

This study examined the effects of heavy-ion radiation on biomolecules at the molecular level. The researchers developed an advanced supersonic gas jet technology to produce clusters of biomolecules attached to water molecules. Pyrimidine, a fundamental structural unit of DNA bases, was selected to simulate DNA in the tissue environment and to investigate its decay mechanism after heavy-ion irradiation.

The experiments were conducted at the experimental cooler storage ring of the Heavy Ion Research Facility in Lanzhou and the 320 kV platform for multi-disciplinary research with highly charged ions. The researchers used carbon and iron ion beams to bombard the clusters of pyrimidine surrounded by water molecules. State-of-the-art quantum chemical calculations were employed to help reveal the decay mechanisms.

The study revealed for the first time that in living tissues irradiated by a heavy-ion beam, inner-valence ionized water can transfer excitation energy to DNA molecules through the ICD process.

“This process not only leads to the ionization of the pyrimidine molecule with emission of a low-energy electron, but also initiates proton transfer between water molecules, resulting in the production of harmful secondary particles—hydroxyl radicals and hydrated protons,” said Prof. Xu Shenyue from IMP, one of the corresponding authors of the study.

This finding challenges the long-held assumption that inner-valence ionized water cations decay through self-fragmentation, with their fragments indirectly affecting DNA. Instead, the observed mechanism shows that these inner-valence ionized water cations can directly interact with DNA through ICD while also releasing harmful secondary particles near DNA. This significantly increases the risk of DNA double-strand breaks.

Furthermore, compared to other types of radiation, heavy-ion irradiation significantly increases the proportion of inner-valence ionization in water molecules, thereby dramatically enhancing its biological effectiveness.

“The observed mechanism is an important factor contributing to the superior biological effects of heavy-ion therapy. It sheds light on the molecular mechanisms of radiation damage and may play an essential role in optimizing radiotherapy techniques in the future,” said Prof. Ma Xinwen from IMP, another corresponding author of the study.