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

描述（由申请人提供）：尽管手术和医学进步，恶性胶质瘤患者的预后仍然严峻。为了应对这一挑战，我们提出了一个计划，将结合-第一次-两个主要的进展，用于治疗弥漫性恶性胶质瘤的技术：靶向胶质瘤干细胞（GSC）和新的基于纳米技术的输送系统设计用于对流增强输送（CED）的新型药物。我们相信基于生物学的设计方法，其中我们选择对脑肿瘤持续存在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的药物的控释纳米颗粒，这些药物被优化用于治疗神经胶质瘤。在这个项目中，我们将测试的假设，载药，聚合物纳米粒子可以通过CED输送到脑肿瘤，并加载这些纳米粒子与药物专门选择其对GSC的生物活性可以提高颅内肿瘤的治疗。我们将通过完成一组相互关联的特定目标来测试这一假设：优化纳米颗粒的性质，以通过CED进行最有效的递送;表征对GSC具有增强活性的新型药物;以及控制递送用于治疗免疫功能低下大鼠颅内人类胶质瘤的新型药物。

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.