Brain Tumor Imaging and Therapy Using Magnetic Nanoparticles

项目4：使用磁性纳米粒子进行脑肿瘤成像和治疗 恶性脑瘤是一种特别难治的癌症，存活率很低。 在过去的几十年里取得了进步。早期诊断的困难和缺乏有效的方法 在脑肿瘤上定位有效的治疗药物的方法是导致这种临床的原因。 困境，源于脑血管的独特结构。血脑屏障(BBB) 脑血管系统由一层连续的脑血管内皮细胞组成，这些细胞 结合在一起的紧密连接，并防止大多数血液传播的药物进入大脑。 因此，脑瘤在早期阶段很难诊断，而且是最具耐药性的肿瘤之一。 去做化疗。手术切除或/和外照射仍然是脑部的标准治疗方法 肿瘤。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，请访问 UNC-CH的组装是为了将纳米技术的最新进展应用于开发新的高效 用于靶向输送成像造影剂和抗癌疗法的磁性纳米矢量 脑瘤。 超小的超顺磁性纳米颗粒已被证明具有更高的交叉倾向。 BBB由于其独特的性质。通过外部设备操纵这些纳米颗粒的能力 磁场为脑肿瘤的靶向输送提供了更大的机会。我们将发展 具有所需表面特征的超顺磁性纳米颗粒，可定向到 使用特制的磁性系统的脑瘤。这些纳米颗粒可以用一种 多种细胞靶向多肽，以增强其在脑瘤新生血管或细胞中的沉积。 新型脑肿瘤特异性多模式成像造影剂和治疗制剂可以是 基于这种超顺磁性纳米颗粒平台通过附着小分子而易于设计 具有成像对比度增强或抗癌特性。我们还将评估这一点的效用 磁性纳米粒靶向递送平台在小鼠脑肿瘤模型中的应用。建议数 因此，跨学科研究计划将纳米技术的最新发展与新的 开展脑肿瘤特异性多模式成像对肿瘤生物学的认识 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，并对实现早期发现和 为脑瘤开发有效的治疗方法。

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.