Department of Nuclear Medicine and Radiobiology, Cancer Research Center, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
Int J Mol Sci. 2023 Feb 28;24(5):4697. doi: 10.3390/ijms24054697.
Metal nanoparticles are considered as highly promising radiosensitizers in cancer radiotherapy. Understanding their radiosensitization mechanisms is critical for future clinical applications. This review is focused on the initial energy deposition by short-range Auger electrons; when high energy radiation is absorbed by gold nanoparticles (GNPs) located near vital biomolecules; such as DNA. Auger electrons and the subsequent production of secondary low energy electrons (LEEs) are responsible for most the ensuing chemical damage near such molecules. We highlight recent progress on DNA damage induced by the LEEs produced abundantly within about 100 nanometers from irradiated GNPs; and by those emitted by high energy electrons and X-rays incident on metal surfaces under differing atmospheric environments. LEEs strongly react within cells; mainly via bound breaking processes due to transient anion formation and dissociative electron attachment. The enhancement of damages induced in plasmid DNA by LEEs; with or without the binding of chemotherapeutic drugs; are explained by the fundamental mechanisms of LEE interactions with simple molecules and specific sites on nucleotides. We address the major challenge of metal nanoparticle and GNP radiosensitization; i.e., to deliver the maximum local dose of radiation to the most sensitive target of cancer cells (i.e., DNA). To achieve this goal the emitted electrons from the absorbed high energy radiation must be short range, and produce a large local density of LEEs, and the initial radiation must have the highest possible absorption coefficient compared to that of soft tissue (e.g., 20-80 keV X-rays).
金属纳米颗粒被认为是癌症放射治疗中极具前途的放射增敏剂。了解它们的放射增敏机制对于未来的临床应用至关重要。本综述重点介绍了短程俄歇电子最初的能量沉积;当高能辐射被位于重要生物分子(如 DNA)附近的金纳米颗粒(GNPs)吸收时。俄歇电子和随后产生的次级低能电子(LEEs)是导致这些分子附近随后发生的大部分化学损伤的原因。我们强调了最近在由辐照 GNPs 附近约 100 纳米范围内大量产生的 LEEs 以及由高能电子和 X 射线在不同大气环境下撞击金属表面产生的 LEEs 引起的 DNA 损伤方面的进展。LEEs 在细胞内强烈反应;主要是由于瞬态阴离子形成和电子离解的键断裂过程。LEEs 诱导质粒 DNA 损伤的增强;无论是否结合化疗药物;都可以通过 LEEs 与简单分子和核苷酸特定位点的相互作用的基本机制来解释。我们解决了金属纳米颗粒和 GNP 放射增敏的主要挑战;即,将最大局部辐射剂量输送到癌细胞最敏感的靶标(即 DNA)。为了实现这一目标,吸收的高能辐射发出的电子必须是短程的,并且产生大量的局部 LEE 密度,并且初始辐射必须具有比软组织(例如,20-80 keV X 射线)尽可能高的吸收系数。