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都依赖于高能辐射的使用。例如，X射线 而γ-射线疗法在肿瘤治疗中也很常见。在有效的同时，健康的组织也暴露在 在这种类型的治疗过程中受到辐射的影响。目前减少患者总辐射剂量的研究努力是 专注于将放射增敏材料运送到癌症部位。这些材料，如金属 纳米颗粒会在局部吸收更多的辐射，从而节省健康组织。耐人寻味的是，这些结果 实验表明，这些纳米粒子的效率高于理论上的预期。 仅仅是辐射吸收的增加。一个有吸引力但未经证实的解释是，低能量 电子(LEE)是由放射增敏材料产生的，大部分局部组织损伤是 是由这些李氏引起的。 在这个项目中，我们直接测量已知放射增敏剂的李氏发射，并将其与细胞相关。 损坏。这将是有史以来第一次对LEE在放射治疗中的作用进行直接评估，并通过 我们研制的一种既能测量X射线诱导的LEE通量又能测量能量的新仪器 放射性同位素-纳米颗粒结合物的辐照或放射性衰变。因为李氏极易导致化学物质 反应，如DNA链断裂，但在溶液中有极短的范围，我们假设 靶向肿瘤细胞中特定隔间的李发射纳米颗粒将使其效果最大化 同时将对健康组织的损害降至最低。我们的LEE发射测量和体外实验将 告知新一代具有高LEE发射的靶向纳米材料的设计。表现最好的 纳米材料随后将在肺癌小鼠模型中进行测试，以评估体内疗效。 总体而言，该项目代表了第一个合理的设计策略，以最大化的治疗效果 辐射增敏纳米材料。

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.