A research team led by Prof. HUANG Qing from the Hefei Institutes of Physical Science of the Chinese Academy of Sciences, in collaboration with the Shanghai Institute of Optics and Fine Mechanics and Shandong University, has found that nanosecond laser-driven proton FLASH radiotherapy can maintain its cancer-killing effect while reducing damage to normal cells.
The study, published in iMed, shows that this new irradiation method protects normal bronchial epithelial cells by preserving mitochondrial function and reducing ferroptosis, an iron-dependent form of cell death.
Radiotherapy is widely used to treat cancer, but radiation can also harm surrounding healthy tissues. FLASH radiotherapy, which delivers radiation at an ultra-high dose rate, has attracted attention because it may reduce normal tissue damage without weakening tumor control.
In this study, the researchers used a laser-driven proton platform to deliver radiation pulses lasting about 12.9 nanoseconds. They compared the effects of this approach with conventional proton irradiation on lung cancer A549 cells and normal bronchial epithelial BEAS-2B cells.
The results showed that both treatments effectively killed cancer cells. However, compared with conventional irradiation, nanosecond FLASH irradiation caused much less damage to normal cells. Further analysis found that FLASH irradiation helped maintain mitochondrial structure and function while reducing ferroptosis.
The researchers also found that conventional irradiation triggered the stress-related protein ATF3 in normal cells, weakening antioxidant defenses and increasing oxidative damage. The extremely short FLASH pulse appeared to limit this stress response, helping normal cells better withstand radiation exposure.
The findings suggest that the way radiation energy is delivered, not only the total dose, plays an important role in determining cellular responses. This work may contribute to the development of safer and more precise radiotherapy approaches.
Schematic of Normal Tissue Sparing in Laser-Proton FLASH-RT (Image by SHAO Changsheng)
