Nanoparticle-Enabled Brain Tumor Surgery

纳米粒子脑肿瘤手术

• 批准号: 7494982
• 负责人: Daniel Orringer
• 金额: $ 5.29万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7494982
• 关键词: Adult; Animal Model; Area; Biophotonics; Blood - brain barrier anatomy; Brain Neoplasms; Cell Line; Cephalic; Characteristics; Childhood; Color; Computers; Data; Development; Dyes; Evaluation; Excision; Extravasation; Eye; Glioma; Goals; Image; Image Analysis; Imagery; In Vitro; Label; Laboratories; Left; Localized; Magnetic Resonance Imaging; Mediating; Methods; Methylene blue; Modeling; Morbidity - disease rate; National Research Service Awards; Nature; Neoplasms; Nerve Tissue; Neurosurgeon; Normal tissue morphology; Operative Surgical Procedures; Optics; Outcome; Patients; Peptides; Qualitative Evaluations; Rattus; Research; Residual Tumors; Residual state; Site; Staining method; Stains; Structure; Techniques; Testing; Therapeutic Index; Time; Tissues; Tumor Cell Line; Tumor Volume; Visual; base; brain tissue; clinically relevant; design; improved; in vivo; iron oxide; mortality; nanodevice; nanoparticle; neoplastic; neoplastic cell; novel; novel strategies; polyacrylamide; research study; size; tumor

DESCRIPTION (provided by applicant): Improvements in the treatment of brain tumors have produced little impact on outcomes over the past three decades. Still, survival for both pediatric and adult brain tumors is known to be maximized by radiographically complete surgical resection. Unfortunately, even with the best microsurgical technique, resection may leave behind residual, MRI-demonstrable tumor. We propose the development of intravenously-administered, dye-labeled nanoparticles selectively targeted to brain tumors that will optimize the ability of neurosurgeons to delineate neoplasm from healthy nervous tissue. By maximizing surgical resection and minimizing adjacent tissue damage, targeted nanoparticles will ultimately improve the treatment of brain tumor patients. The proposed nanoparticles will consist of a biodegradable polyacrylamide core containing an optical dye. The nanoparticle size (30-70 nm) has been designed to allow extravasation across areas of blood brain barrier breakdown characteristic of tumors, while minimizing passage across an intact blood-brain barrier. The localization of nanoparticles at tumor sites will be optimized by coating nanoparticles tumor-homing F3 peptide. We have previously demonstrated the high therapeutic index, nontoxicity and bioelimination of similar nanoparticles. The ability of multifunctional nanoparticles to enable intraoperative optical delineation will be tested in several animal models of glioma. Qualitative evaluation of targeted nanoparticle-mediated delineation will be carried out in the rat cranial window model because it allows real-time, in vivo visualization of superficial experimental gliomas. These experiments will allow us to accurately characterize the nature of the contrast that the nanoparticles will provide with respect to surrounding viable brain tissue. Quantitave evaluation will utilize computer-based image analysis techniques to compare targeted nanoparticle-based estimates tumor volume with clinically-relevant, MRI-based estimates of tumor volume. In summary, this proposal introduces a novel approach to enhancing brain tumor surgery, via biophotonic nanodevices previously developed in our laboratories. The proposed nanodevices are expected to dramatically improve the treatment of brain tumors by developing novel methods for intraoperative visual imaging. The ultimate goal is to reduce morbidity and mortality in brain tumor patients by maximizing surgical precision.

描述（由申请人提供）：在过去的三十年中，脑肿瘤治疗的改善对结果的影响很小。尽管如此，已知小儿和成人脑肿瘤的生存均通过射线照相完整的手术切除最大化。不幸的是，即使采用了最佳的显微外科技术，切除也可能留下残留的MRI可示威肿瘤。我们提出，静脉注射，染料标记的纳米颗粒的发展有选择地针对脑肿瘤，这些纳米颗粒将优化神经外科医生从健康的神经组织中划定肿瘤的能力。通过最大化手术切除并最大程度地减少相邻组织损伤，靶向纳米颗粒最终将改善对脑肿瘤患者的治疗。所提出的纳米颗粒将由含有光学染料的可生物降解的聚丙烯酰胺芯组成。纳米颗粒的大小（30-70 nm）旨在使肿瘤的血脑屏障分解特征渗出，同时最大程度地减少对完整的血脑屏障的传递。纳米颗粒在肿瘤部位的定位将通过涂层纳米颗粒肿瘤为肿瘤的F3肽来优化。我们以前已经证明了类似纳米颗粒的高治疗指数，无毒性和生物脱位。多功能纳米颗粒使术中光学描述的能力将在几种神经胶质瘤动物模型中进行测试。对靶向纳米粒子介导的描述的定性评估将在大鼠颅窗模型中进行，因为它允许实时，体内可视化浅表实验性神经胶质瘤。这些实验将使我们能够准确地表征纳米颗粒相对于周围可行的脑组织提供的对比的性质。定量评估将利用基于计算机的图像分析技术来比较靶向纳米颗粒的估计量与临床相关的基于MRI的肿瘤量估计值。总而言之，该提案通过以前在我们的实验室中开发的生物光纳米版本引入了一种新的方法来增强脑肿瘤手术。预计提出的纳米版本将通过开发用于术中视觉成像的新方法来大大改善脑肿瘤的治疗方法。最终目标是通过最大化手术精度来降低脑肿瘤患者的发病率和死亡率。