Brain Tumor Imaging and Therapy Using Magnetic Nanoparticles

项目4：使用磁性纳米颗粒的脑肿瘤成像和治疗 恶性脑肿瘤是一种特别棘手的癌症，几乎没有存活率 在过去的几十年里，改善。早期诊断的困难和缺乏有效的 将有效治疗剂定位在脑肿瘤上的方法负责这种临床治疗。 这是一个两难的问题，它源于脑血管的独特结构。血脑屏障（BBB） 脑血管系统由连续的脑血管内皮细胞层组成， 通过紧密连接结合在一起，并阻止大多数血液传播剂进入大脑。 因此，脑肿瘤在早期阶段很难诊断，并且是最具抵抗力的肿瘤之一 到化疗。手术切除或/和外部放射仍然是脑肿瘤的标准治疗方法。 肿瘤的作为卡罗莱纳癌症纳米技术卓越中心（CCCNE）的一部分， 来自不同学科（化学、物理、遗传学、肿瘤学和放射学）的研究人员， UNC-CH是组装应用纳米技术的最新进展，在开发新的高效 用于靶向递送成像造影剂和抗癌疗法的磁性纳米载体， 脑瘤 超小的超顺磁性纳米粒子已被证明具有更高的交叉倾向 由于其独特的性质，BBB。用外部的纳米粒子来操纵这些纳米粒子的能力 磁场为脑肿瘤的靶向递送提供了更大的机会。我们将开发 超顺磁性纳米颗粒具有所需的表面特性，其可以被引导到 使用设计的磁系统来治疗脑瘤。这些纳米颗粒可以进一步用以下物质修饰： 多种细胞靶向肽，以增强其在脑肿瘤新血管或细胞中的沉积。 新的脑肿瘤特异性多模态成像造影剂和治疗制剂可以 基于这种超顺磁性纳米颗粒平台， 具有成像对比度增强或抗癌特性。我们还将评估其效用 磁性纳米颗粒靶向递送平台在小鼠模型的脑肿瘤中的应用。拟议 跨学科的研究计划，从而结合了纳米技术的最新发展与新的 对肿瘤生物学的理解，努力开发脑肿瘤特异性多模态成像 造影剂和治疗制剂。该项目的成功将带来新的创新 癌症研究的方法，并在实现早期发现和 开发有效的治疗脑瘤的方法

Project 4: Brain Tumor Imaging and Therapy Using Magnetic Nanoparticles Malignant brain tumors are a particularly intractable form of cancer that has seen little survival improvement over the past few decades. The difficulty in early diagnosis of and the lack of efficient means of localizing effective therapeutic agents on the brain tumors are responsible for this clinical dilemma, which stems from the unique structure of brain vasculatures. The blood-brain barrier (BBB) in the brain vasculature consists of a continuous layer of cerebral vascular endothelial cells that are bound together with tight junctions, and prevents the access of most blood-borne agents to the brain. As a result, brain tumors are difficult to diagnose in their early stage and are among the most resistant to chemotherapy. Surgical resection or/and external radiation remains the standard treatment for brain tumors. As a part of Carolina Center of Cancer Nanotechnology Excellence (CCCNE), a team of investigators from diverse disciplines (Chemistry, Physics, Genetics, Oncology, and Radiology) at UNC-CH is assembled to apply the latest advances in nanotechnology in developing new efficient magnetic nanovectors for targeted delivery of imaging contrast agents and anticancer therapies to brain tumors. Ultrasmall superparamagnetic nanoparticles have been shown to have higher propensity of crossing the BBB owing to their unique properties. The ability to manipulate these nanoparticles with an external magnetic field offers even greater opportunities in targeted delivery to brain tumors. We will develop superparamagnetic nanoparticles with desired surface characteristics which can be directed to the brain tumors using a designer magnetic system. These nanoparticles can be further modified with a variety of cell-targeting peptides to enhance their deposition in brain tumor neovasculatures or cells. Novel brain tumor-specific multi-modality imaging contrast agents and therapeutic formulations can be readily designed based on this superparamagnetic nanoparticle platform by attaching small molecules with imaging contrast enhancement or anti-cancer properties. We will also evaluate the utility of this magnetic nanoparticle targeted delivery platform in brain tumors of a mouse model. The proposed interdisciplinary research program thus combines the latest developments in nanotechnology with new understandings of tumor biology in an effort to develop brain tumor-specific multi-modality imaging contrast agents and therapeutic formulations. The success of this project will lead to new innovative approaches to cancer research, and have significant implications in realizing early detection and developing effective therapies for brain tumors.