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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