CED of Nanoparticles Loading with Novel Agents for Improved Treatment of Gliomas

载有新型药物的纳米颗粒的 CED 可改善神经胶质瘤的治疗

• 批准号: 8107039
• 负责人: W. Mark Saltzman
• 金额: $ 30.91万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8107039
• 关键词: Address; Adult; Animals; Biological; Biology; Brain; Brain Neoplasms; Caliber; Camptothecin; Cells; Chemistry; Convection; Development; Diagnosis; Diffuse; Diffusion; Dose; Drug Delivery Systems; Exhibits; FDA approved; Glioma; Growth; Human; Immunocompromised Host; Intracranial Neoplasms; Lead; Libraries; Malignant Glioma; Malignant neoplasm of brain; Medical; Methods; Nanotechnology; New Agents; Operative Surgical Procedures; Patients; Penetration; Pharmaceutical Preparations; Polymers; Property; Rattus; Research Project Grants; Sampling; Screening procedure; Solid; Stem cells; Surface; System; Technology; Testing; Time; Tumor Stem Cells; Tumor-Derived; United States; Work; base; biodegradable polymer; controlled release; design; drug distribution; drug efficacy; efficacy testing; improved; interdisciplinary approach; interest; nanoparticle; novel; outcome forecast; particle; prevent; programs; response; self-renewal; temozolomide; tumor; uptake

DESCRIPTION (provided by applicant): Despite surgical and medical advances, the prognosis for patients with malignant gliomas remains grim. To address this challenge, we propose a program that will combine-for the first time-two major advances in technology for treating diffuse malignant glioma: novel drugs that target glioma stem cells (GSCs) and new nanotechnology-based delivery systems designed for use with convection-enhanced delivery (CED). We believe a biology-based design approach, in which we select drugs that have high activity against the cells that are most important in the persistence of brain tumors, will allow us to design controlled release nanoparticles for CED of drugs that are optimized for the treatment of gliomas. In this project, we will test the hypothesis that drug-loaded, polymer nanoparticles can be delivered to brain tumors by CED, and that loading these nanoparticles with drugs specifically selected for their biological activity against GSCs can enhance treatment of intracranial tumors. We will test this hypothesis by completion of an inter-related set of specific aims: optimization of the properties of nanoparticles for most effective delivery via CED; characterization of novel agents with enhanced activity against GSCs; and controlled delivery of novel agents for treatment of intracranial human gliomas in immunocompromised rats. PUBLIC HEALTH RELEVANCE: Malignant gliomas are the most common primary malignant brain tumors in adults. More than 15,000 new cases are diagnosed in the United States each year. This research project will result in the development of new methods for the treatment of malignant gliomas.

描述（由申请人提供）：尽管外科和医学取得了进步，但恶性神经胶质瘤患者的预后仍然严峻。为了应对这一挑战，我们提出了一项计划，该计划将首次结合治疗弥漫性恶性神经胶质瘤的两项重大技术进步：针对神经胶质瘤干细胞（GSC）的新药物和设计用于治疗的基于纳米技术的新型输送系统对流增强输送（CED）。我们相信，基于生物学的设计方法，即我们选择对脑肿瘤持续存在中最重要的细胞具有高活性的药物，将使我们能够设计用于 CED 药物的控释纳米颗粒，并针对治疗进行优化神经胶质瘤。在这个项目中，我们将测试这样一个假设：载药聚合物纳米颗粒可以通过 CED 递送至脑肿瘤，并且在这些纳米颗粒上装载专门针对 GSC 生物活性而选择的药物可以增强对颅内肿瘤的治疗。我们将通过完成一组相互关联的具体目标来检验这一假设：优化纳米粒子的特性，以通过 CED 最有效地传递；具有增强的抗 GSC 活性的新型药物的表征；以及用于治疗免疫功能低下大鼠颅内人类神经胶质瘤的新型药物的受控递送。 公共卫生相关性：恶性神经胶质瘤是成人中最常见的原发性恶性脑肿瘤。美国每年诊断出超过 15,000 例新病例。该研究项目将开发治疗恶性神经胶质瘤的新方法。