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: 8620614
• 负责人: W. Mark Saltzman
• 金额: $ 33.31万
• 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/8620614
• 关键词: Address; Adult; Animals; Biological; Biology; Brain; Brain Neoplasms; Caliber; Camptothecin; Cells; Chemistry; Convection; Development; Diagnosis; Diffuse; Diffusion; Dose; Drug Delivery Systems; Drug Targeting; 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; 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; public health relevance; response; screening; 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.

描述（由申请人提供）：尽管手术和医疗进展，但针对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，该计划将结合第两个用于治疗弥漫性恶性神经胶质瘤技术的主要进步：针对胶质瘤干细胞（GSC）和新的基于纳米技术的新型药物，该药物旨在与对流增强输送（CED）一起使用。我们认为，一种基于生物学的设计方法，在这种方法中，我们选择对在脑肿瘤持久性中最重要的细胞具有较高活性的药物，将使我们能够为用于治疗神经胶质瘤的药物的CED设计受控的释放纳米颗粒。在该项目中，我们将测试以下假设：可以通过CED将药物负载的聚合物纳米颗粒递送到脑肿瘤中，并且将这些纳米颗粒加载的药物专门用于针对GSC的生物学活性可以增强颅内肿瘤的治疗。我们将通过完成一组相互关联的特定目的来检验这一假设：通过CED优化纳米颗粒的性质，以最有效地递送；对GSC活性增强的新型药物的表征；并控制了新型药物在免疫功能低下的大鼠中治疗颅内人神经胶质瘤的递送。