Trimetallic Nitride Templated Endohedral Metallofullerenes as Dual Imaging and Mu

三金属氮化物模板内嵌金属富勒烯作为双成像和 Mu

• 批准号: 7514631
• 负责人: Marissa Nichole Rylander
• 金额: $ 20.25万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-15 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7514631
• 关键词: Biomedical Engineering; Carbon; Carbon Nanotubes; Cell Death; Cells; Class; Complication; Contrast Media; Dependence; Deposition; Development; Diagnostic; Diffusion; Disease; Dose; Effectiveness; Encapsulated; Engineering; Enhancers; Environment; Excision; Exhibits; Fever; Fluorescence; Fullerenes; Funding; Future; Gadolinium; Generations; Goals; Heat shock proteins; Heating; Holmium; Hydroxyl Radical; Image; Individual; Induced Hyperthermia; Infrared Rays; Injury; Invasive; Ions; Lasers; Lead; Length of Stay; Lesion; Light; Low-Level Laser Therapy; Lutetium; Magnetic Resonance Imaging; Malignant Neoplasms; Measurement; Measures; Mechanics; Medicine; Metabolic; Metals; Molecular; Molecular Chaperones; Multimodal Imaging; Operative Surgical Procedures; Optics; Patients; Postdoctoral Fellow; Process; Property; Range; Rate; Reactive Oxygen Species; Recovery; Recurrence; Relative (related person); Research; Research Personnel; Resistance; Shapes; Singlet Oxygen; Structure; Superoxides; Temperature; Terbium; Therapeutic; Therapeutic Agents; Therapeutic heat application; Thermal Conductivity; Time; Tissues; Toxic effect; Tumor Tissue; Water; Work; absorption; base; brain tissue; cancer therapy; cell injury; cytotoxicity; design; hyperthermia treatment; improved; innovation; irradiation; member; multidisciplinary; nano; nanomaterials; nanoparticle; nanoprobe; nanoscale; nanoshell; neoplastic cell; novel; novel diagnostics; outcome forecast; particle; protein expression; radiochemical; response; therapeutic effectiveness; tumor; tumor eradication

DESCRIPTION (provided by applicant): The project objective is to investigate a novel class of fullerenes called trimetallic nitride templated endohedral metallofullerenes (TNT EMFs) as dual imaging and multimodal therapeutic agents for laser cancer therapy. We will investigate the therapeutic effectiveness of TNT EMFs of the form Gd3N@C80 independently and in a peapod arrangement (Gd3N@C80 molecules within single- walled carbon nanotubes) denoted as Gd3N@C80-peapods in cancer laser induced hyperthermia therapy. These particles have been previously demonstrated as exceptional magnetic resonance imaging contrast agents due to their superior relaxivity and lower diffusion and elimination rates as compared to gadolinium. Therefore, lower concentrations of contrast agent are required thereby reducing potential toxicity. Although Gd3N@C80 have been shown to be superior imaging agents, they also have tremendous therapeutic potential which merits exploration. Gd3N@C80 possesses an absorption peak within the infrared spectrum at approximately 1050 nm at which wavelength other TNT EMFs and carbon nanotubes have been found to absorb light and generate heat. Fullerenes and metallofullerenes also generate singlet oxygen when exposed to infrared radiation permitting targeted cell cytotoxicity (5). This proposal will evaluate the therapeutic potential of Gd3N@C80 in laser therapy by measuring the thermal enhancing (ability to generate heat) and photo-toxicity (generation of reactive oxygen species) of these particles following laser excitation. Both mechanisms if directed properly can lead to cytotoxicity. The thermal sensitizing effect of Gd3N@C80 will be determined by 1) measuring heat delivery, cell death, and HSP expression following laser irradiation of cells with inclusion of Gd3N@C80-peapods and 2) characterizing the change in optical and thermal properties, temperature, cellular injury, and HSP expression distribution dependence on Gd3N@C80-peapod properties, concentration, and distribution in tissue representative phantoms. The photo-toxicity of Gd3N@C80-peapods by measuring generation of reactive oxygen species (ROS), singlet oxygen (1O2), superoxide (O2-.), and hydroxyl radical (.OH) following laser excitation of cells. Completion of this research will permit determination of the therapeutic utility of Gd3N@C80-peapods in cancer therapy and permit optimization of their properties and laser parameters to permit maximum tumor destruction. Development of dual diagnostic and therapeutic agents for cancer with heightened sensitivity, selectivity, and lower toxicity could greatly enhance the prognosis of patients suffering from this disease. The goal of this project is to explore the feasibility of employing a novel class of fullerenes called trimetallic nitride templated endohedral metallofullerenes (TNT EMFs) as dual imaging and multimodal therapeutic agents in cancer laser therapy. By integrating TNT EMFs with laser heating, lower thermal doses can be employed and more selective heating achieved, thereby permitting more precise control of the thermal energy delivery ultimately permitting effective tumor eradication while minimizing healthy tissue destruction.

项目描述（由申请人提供）：项目目标是研究一种新型的富勒烯，称为三金属氮化模板内生金属富勒烯（TNT EMFs），作为激光癌症治疗的双重成像和多模式治疗剂。我们将研究形式为Gd3N@C80和豆荚状排列（Gd3N@C80分子在单壁碳纳米管内）的TNT电磁场在癌症激光诱导热疗中的治疗效果，表示为Gd3N@C80-peapods。与钆相比，这些颗粒具有优越的弛豫性和较低的扩散和消除速率，因此已被证明是特殊的磁共振成像造影剂。因此，需要较低浓度的造影剂，从而降低潜在的毒性。虽然Gd3N@C80已被证明是优越的显像剂，但它们也有巨大的治疗潜力，值得探索。Gd3N@C80在红外光谱中约1050 nm处有一个吸收峰，在该波长处发现了其他TNT emf和碳纳米管吸收光并产生热。富勒烯和金属富勒烯在暴露于红外辐射时也会产生单线态氧，从而产生靶向细胞毒性(5)。该提案将通过测量激光激发后这些粒子的热增强（产生热量的能力）和光毒性（产生活性氧）来评估Gd3N@C80在激光治疗中的治疗潜力。如果指导得当，这两种机制都可以导致细胞毒性。Gd3N@C80的热敏效应将通过以下方式确定：1)测量含有Gd3N@C80-peapods的细胞在激光照射后的热传递、细胞死亡和热休克蛋白表达；2)表征光学和热性质、温度、细胞损伤和热休克蛋白表达分布的变化，这些变化依赖于Gd3N@C80-peapod的性质、浓度和组织代表性幻影中的分布。通过测量激光激发细胞后活性氧（ROS）、单线态氧（1O2）、超氧化物（O2-）和羟基自由基（. oh）的生成，研究Gd3N@C80-peapods的光毒性。这项研究的完成将允许确定Gd3N@C80-peapods在癌症治疗中的治疗效用，并允许优化其特性和激光参数，以最大限度地破坏肿瘤。开发具有高敏感性、选择性和低毒性的双重诊断和治疗药物，可以大大提高癌症患者的预后。该项目的目标是探索在癌症激光治疗中使用一种称为三金属氮化模板内生金属富勒烯（TNT EMFs）的新型富勒烯作为双重成像和多模式治疗剂的可行性。通过将TNT电磁场与激光加热相结合，可以使用更低的热剂量，实现更有选择性的加热，从而可以更精确地控制热能输送，最终实现有效的肿瘤根除，同时最大限度地减少健康组织的破坏。