A surface chemistry guided approach to the rational design of low-energy electron emitting nanomaterials

项目摘要/摘要 医学成像和治疗的许多方面依赖于高能辐射的使用。例如x射线 和γ射线疗法通常用于治疗肿瘤。虽然有效，但健康组织也暴露在 在这种治疗过程中的辐射。目前的研究努力，以减少总辐射剂量的病人是 专注于将放射增敏材料输送到癌症部位。这些材料，如金属 纳米颗粒，局部吸收更多的辐射，保护健康组织。有趣的是，这些结果 实验表明，这些纳米颗粒的功效高于理论预期， 辐射吸收的增加。一个有吸引力但未经证实的解释是， 电子（LEE）是由放射增敏材料产生的，并且大多数局部组织损伤是 造成的。 在本项目中，我们直接测量已知放射增敏剂的LEE发射，并将其与细胞相关 损害这将是有史以来第一次直接评估LEE在放射治疗中的作用， 我们研制了一种新的仪器，可以测量X射线诱导的LEE通量和能量 放射性同位素-纳米颗粒缀合物的辐射或放射性衰变。因为LEE很容易引起化学反应， 反应，如DNA链断裂，但在溶液中具有极短的范围，我们假设， 将LEE发射纳米颗粒靶向肿瘤细胞中的特定区室将使其有效性最大化 同时最大限度地减少对健康组织的损害。我们的LEE发射测量和体外实验将 为设计新一代具有高LEE排放的目标纳米材料提供信息。表现最好的 随后将在肺癌小鼠模型中测试纳米材料，以评估体内功效。 总的来说，该项目代表了第一个合理的设计策略，以最大限度地提高治疗效果， 放射增敏纳米材料

Project Abstract/Summary Many aspects of medical imaging and treatment rely on the use of high-energy radiation. For example, X-ray and γ-ray therapies are common for the treatment of tumors. While effective, healthy tissues are also exposed to radiation during this type of treatment. Current research efforts to reduce total radiation doses to patients are focused on delivering radiosensitization materials to cancerous sites. These materials, such as metal nanoparticles, adsorb more of the radiation locally and spare heathy tissue. Intriguingly, the results of these experiments indicate that the efficacies of these nanoparticles are higher than would be expected theoretically from just an increase in radiation adsorption. One attractive, but unproven, explanation is that low-energy electrons (LEEs) are generated by the radiosensitization materials and most of the local tissue damage is caused by these LEEs. In this project, we directly measure LEE emission from known radiosensitizers, which we will correlate to cell damage. This will be the first-ever direct assessment of the roles of LEEs in radiotherapy, and is enabled by a new instrument we have developed that can measure both the flux and energy of LEEs induced by X-ray irradiation or radioactive decay of radioisotope-nanoparticle conjugates. Because LEEs readily cause chemical reactions such as DNA strand breaks but have an extremely short range in solution, we hypothesize that targeting LEE-emitting nanoparticles to specific compartments in tumor cells will maximize their effectiveness while minimizing damage to healthy tissues. Our LEE emission measurements and in vitro experiments will inform the design of a new generation of targeted nanomaterials with high LEE emission. The best-performing nanomaterials will subsequently be tested in a mouse model of lung cancer to evaluate in vivo efficacy. Overall, this project represents the first rational design strategy for maximizing the therapeutic effect of radiosensitizing nanomaterials.