Nanoparticle-Enabled Brain Tumor Surgery

描述(由申请人提供)：在过去的三十年里，脑瘤治疗的改进对结果几乎没有影响。尽管如此，众所周知，通过放射学上的完全手术切除，儿童和成人脑肿瘤的存活率都是最大的。不幸的是，即使采用最好的显微外科技术，切除也可能留下MRI可显示的残留肿瘤。我们建议开发静脉给药、染料标记的纳米颗粒，选择性地针对脑肿瘤，这将优化神经外科医生从健康神经组织中描绘肿瘤的能力。通过最大限度地扩大手术切除和最大限度地减少邻近组织损伤，靶向纳米颗粒最终将改善脑肿瘤患者的治疗。提议的纳米颗粒将由一个含有光学染料的可生物降解的聚丙烯酰胺核组成。这种纳米颗粒尺寸(30-70 nm)被设计成允许渗入肿瘤特有的血脑屏障破坏区域，同时最大限度地减少穿过完整的血脑屏障。纳米粒子在肿瘤部位的定位将通过包裹纳米粒子肿瘤归巢F3多肽来优化。我们之前已经证明了类似纳米粒的高治疗指数、无毒性和生物消除。多功能纳米颗粒能够实现术中光学描绘的能力将在几个胶质瘤动物模型中进行测试。靶向纳米颗粒介导的描绘将在大鼠颅窗模型中进行定性评估，因为它允许对浅层实验性胶质瘤进行实时、活体可视化。这些实验将使我们能够准确地描述纳米颗粒相对于周围存活的脑组织所提供的对比的性质。Quantitave评估将利用基于计算机的图像分析技术来比较基于纳米颗粒的有针对性的肿瘤体积估计值与基于临床相关的、基于MRI的肿瘤体积估计值。综上所述，这项建议引入了一种新的方法，通过我们实验室以前开发的生物光子学纳米设备来加强脑肿瘤手术。所提出的纳米设备有望通过发展术中视觉成像的新方法来显著改善脑肿瘤的治疗。最终目标是通过最大限度地提高手术精度来降低脑肿瘤患者的发病率和死亡率。

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.