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

表面化学引导的低能电子发射纳米材料合理设计方法

基本信息

批准号：
10204451
负责人：
Charles R Mace
金额：
$ 63.21万
依托单位：
TUFTS UNIVERSITY MEDFORD
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-21 至 2022-09-20
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10204451
关键词：
Address Adsorption Affect Animal Cancer Model Animal Model Biologic Characteristic Biological Biological Assay Cancerous Cell Culture Techniques Cell Line Cells Cellular biology Chemicals Chemistry Clinic Clinical Clinical Trials DNA Double Strand Break DNA strand break Data Dose Effectiveness Electromagnetic Energy Exposure to External Beam Radiation Therapy FarGo Formulation Gamma Rays Generations Gold Harm Reduction Human In Vitro Ligands Link Location Malignant neoplasm of lung Measurement Measures Medical Imaging Metals Methods Modeling Nanosphere Non-Small-Cell Lung Carcinoma Oncology Organelles Pathway interactions Patients Performance Peripheral Physics Production Property Radiation Radiation Dose Unit Radiation Oncology Radiation therapy Radiation-Sensitizing Agents Radioactive Radioisotopes Radiosensitization Research Roentgen Rays Role Shapes Site Source Surface Testing Therapeutic Therapeutic Effect Time Tissues Toxic effect Translations Work absorption base cell injury chemical reaction clinical efficacy common treatment design electron energy experimental study improved in vivo insight instrument instrumentation mouse model multidisciplinary nanoGold nanomaterials nanoparticle neoplastic cell next generation novel novel strategies particle performance tests prevent side effect solid state tumor tumor growth x-ray irradiation

项目摘要

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.

项目摘要/总结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 γ射线疗法常用于治疗肿瘤。虽然有效，但健康组织也会暴露在此类治疗期间接受放射治疗。目前减少患者总辐射剂量的研究工作是专注于向癌症部位提供放射增敏材料。这些材料，例如金属纳米粒子，局部吸收更多的辐射并保护健康组织。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上的预期仅来自辐射吸收的增加。一种有吸引力但未经证实的解释是低能量电子（LEE）由放射增敏材料产生，大部分局部组织损伤是由这些LEE引起。在这个项目中，我们直接测量已知放射增敏剂的 LEE 发射，我们将其与细胞相关联损害。这将是首次直接评估 LEE 在放射治疗中的作用，并由我们开发的新仪器可以测量 X 射线引起的 LEE 的通量和能量放射性同位素-纳米粒子缀合物的辐照或放射性衰变。因为 LEE 很容易引起化学反应 DNA 链断裂等反应，但在溶液中的范围极短，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最大限度地提高其有效性同时最大限度地减少对健康组织的损害。我们的 LEE 排放测量和体外实验将为具有高LEE排放的新一代靶向纳米材料的设计提供信息。表现最好的随后将在小鼠肺癌模型中测试纳米材料，以评估体内功效。总体而言，该项目代表了第一个最大化治疗效果的合理设计策略放射增敏纳米材料。