Radiation and Receptor Targeted RadioTheranostic Nanoparticles for Glioblastoma

描述（由申请人提供）：WHO四级胶质瘤：多形性胶质母细胞瘤（GBM）是成人最常见和致命的原发性脑癌。目前GBM的标准治疗包括手术后化疗和放疗联合治疗（RT）；尽管采用了这种积极的方法，中位生存时间仍然只有一年多一点。因此，本研究计划的主要目标是开发一种新的“放射治疗”方法来治疗GBM，该方法首次采用金和超顺磁性氧化铁（SPIO）纳米颗粒负载聚合物胶束（gsm），并利用辐射和glioma限制性il13ra2靶向配体选择性地递送辐射增强和mr成像纳米颗粒。由于具有良好的放射治疗和诊断（放射治疗）特性，gsm将被定制，表征和建模用于颅内肿瘤治疗和成像。分析将包括精确递送RT在增加脑肿瘤内空间靶向GSM积累方面的影响。利用我们在放射生物学，神经肿瘤学，原位和转基因胶质瘤模型，分子成像，纳米技术和生物工程方面的综合专业知识，我们将测试新的GSM配方的管理将显著提高RT治疗GBM的靶向性和有效性，几乎没有增加毒性，并实现以下具体目标目标1。合成和表征具有互补治疗和诊断能力的gsm。目标2。确定放疗和GSM给药之间的最佳时间，以获得颅内肿瘤内最大的选择性GSM积累、MR成像和放疗剂量增强。目标3。描述il13ra2靶向gsm在胶质母细胞瘤成像和治疗中的应用。我们已经组建了一支多才多艺的团队，他们具备必要的经验和专业知识，可以成功地测试我们的假设并实现我们的具体目标。这些研究共同有助于促进GBM治疗的突破性进展，同时有助于实现gsm对这种高度难治性和致命的脑肿瘤的放射治疗潜力。

DESCRIPTION (provided by applicant): WHO Grade IV Glioma: Glioblastoma multiforme (GBM) is the most common and deadly form of primary brain cancer in adults. The current standard treatment of GBM consists of surgery followed by combined chemo- and radiation therapy (RT); despite this aggressive approach, the median survival time remains just over one year. The primary goal of this research proposal is to therefore develop a novel "RadioTheranostic" approach to treat GBM that employs for the first time Gold- and SuperParamagnetic Iron Oxide (SPIO)-nanoparticle loaded polymeric Micelles (GSMs) and utilizes Radiation and a Glioma-restricted IL13Ra2-targeting ligand to selectively deliver radiation-enhancing and MR-imagable nanoparticles. With well aligned radiotherapeutic and diagnostic (RadioTheranostic) properties, GSMs will be customized, characterized and modeled for intracranial tumor treatment and imaging. The analyses will include the effects of precisely delivered RT in augmenting spatially targeted GSM accumulation within brain tumors. Leveraging our combined expertise in radiobiology, neuro-oncology, orthotopic and transgenic glioma models, molecular imaging, nanotechnology and bioengineering we will test the central hypothesis that administration of novel GSM formulations will significantly improve the targeting and efficacy of RT for GBM with little to no added toxicity and fulfill the following specific aims Aim 1. Synthesize and characterize GSMs with complementary therapeutic and diagnostic capabilities. Aim 2. Determine the optimal timing between RT and GSM administration for maximal selective GSM accumulation within intracranial tumors, MR imaging, and RT dose enhancement. Aim 3. Characterize IL13Ra2-targeted GSMs for imaging and treatment of Glioblastoma. We have marshaled a versatile team with the requisite experience and expertise to successfully test our hypothesis and address our specific aims. These studies together should together help facilitate a breakthrough advance in the treatment of GBM, while helping to fulfill the RadioTheranostic potential of GSMs for this highly intractable and deadly brain tumor.