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

描述（由申请人提供）：尽管外科和医学进步，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，该计划将首次结合治疗弥漫性恶性胶质瘤的两项主要技术进展：针对胶质瘤干细胞（GSCs）的新型药物和设计用于对流增强传递（CED）的基于纳米技术的新传递系统。我们相信，基于生物学的设计方法，即选择对脑肿瘤持续存在最重要的细胞具有高活性的药物，将使我们能够设计出用于CED药物的可控释放纳米颗粒，从而优化治疗胶质瘤。在这个项目中，我们将测试一个假设，即载药的聚合物纳米颗粒可以通过CED传递到脑肿瘤，并且在这些纳米颗粒上装载特异性选择的针对GSCs的生物活性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特定目标来验证这一假设：优化纳米粒子的特性，使其通过CED最有效地输送；增强抗GSCs活性的新型药物的表征；以及免疫功能低下大鼠治疗颅内胶质瘤的新型药物的控制递送。

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.