Abstract
The killing of tumor cells by ionizing radiation beams in cancer radiotherapy is currently based on a rather empirical understanding of the basic mechanisms and effectiveness of DNA damage by radiation. By contrast, the mechanical behaviour of DNA encompassing sequence sensitivity and elastic transitions to plastic responses is much better understood. A novel approach is proposed here based on a micromechanical Silicon Nanotweezers device. This instrument allows the detailed biomechanical characterization of a DNA bundle exposed to an ionizing radiation beam delivered here by a therapeutic linear particle accelerator (LINAC). The micromechanical device endures the harsh environment of radiation beams and still retains molecular-level detection accuracy. In this study, the first real-time observation of DNA damage by ionizing radiation is demonstrated. The DNA bundle degradation is detected by the micromechanical device as a reduction of the bundle stiffness, and a theoretical model provides an interpretation of the results. These first real-time observations pave the way for both fundamental and clinical studies of DNA degradation mechanisms under ionizing radiation for improved tumor treatment.
Highlights
In the early days of radiotherapy, very little was known about the mechanism of action mechanism of ionizing radiation and its side effects, sometimes leading to disastrous results
As radiation does not distinguish between healthy and tumor cells, the largest improvement in radiotherapy technology in modern days has concentrated on improving the precision of dose-delivery in space and time, with considerably less interest in the fundamental understanding of the basic mechanisms of biological radiation damage
We introduce and fully characterize a mechanical systems (MEMS)-based device, the Silicon Nanotweezers (SNT)[13], as an ideal instrument to perform the unprecedented real-time biomechanical detection of the radiation damage of DNA exposed to the ionizing radiation environment of radiotherapy treatment
Summary
In the early days of radiotherapy, very little was known about the mechanism of action mechanism of ionizing radiation and its side effects, sometimes leading to disastrous results. Among the main experimental tools adopted up until now to study radiation damage in DNA at the molecular level, we find gas chromatography with ion-selective mass spectrometry[3], highperformance liquid chromatography[4], and electron paramagnetic spin resonance[5,6] All such methods are based on chemical treatments performed on DNA after irradiation. We introduce and fully characterize a MEMS-based device, the Silicon Nanotweezers (SNT)[13], as an ideal instrument to perform the unprecedented real-time biomechanical detection of the radiation damage of DNA exposed to the ionizing radiation environment of radiotherapy treatment. Under well-known and fully (stiffness and viscosity) can be extracted in real-time by using the following equations: characterized irradiation conditions provided by clinical radiotherapy machines, individual DNA strands in the bundle will accumulate damage and break, progressively reducing the bundle mechanical strength.
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