Nanoparticle Enabled Intraoperative Imaging and Therapy

纳米颗粒实现术中成像和治疗

• 批准号: 7881029
• 负责人: Raoul Kopelman
• 金额: $ 11.35万
• 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: 2007-09-30 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7881029
• 关键词: Adjuvant; Adjuvant Chemotherapy; Adult; Adverse effects; Animal Model; Animal Testing; Area; Blood - brain barrier anatomy; Brain Neoplasms; Cell Line; Cephalic; Characteristics; Chemistry; Childhood; Clinical; Development; Dose; Dyes; Evaluation; Excision; Extravasation; Glioma; Goals; Human; Image; In Vitro; Label; Lasers; Left; Light; Magnetic Resonance Imaging; Malignant - descriptor; Malignant neoplasm of brain; Mediating; Methods; Microscopic; Modality; Modeling; Nanotechnology; Neoplasms; Nerve Tissue; Neurosurgeon; Normal tissue morphology; Operative Surgical Procedures; Optics; Outcome; Outsourcing; Patients; Peptides; Phase; Photochemotherapy; Photosensitizing Agents; Phototoxicity; Physics; Protocols documentation; Radiation; Rattus; Reagent; Reporting; Research; Research Personnel; Resectable; Residual Tumors; Residual state; Rodent; Site; Staging; Staining method; Stains; Techniques; Testing; Therapeutic Index; Time; Tissues; Toxic effect; Unresectable; Visual; Work; base; design; gliosarcoma; improved; in vivo; intraoperative imaging; manufacturing scale-up; nanoparticle; neoplastic; neuropathology; neurosurgery; neurotoxicology; novel; novel strategies; nucleolin; polyacrylamide; preference; statistics; tumor

DESCRIPTION (provided by applicant): Improvements in the treatment of brain tumors have produced little impact on outcomes over the past three decades. We propose the development of targeted, multifunctional nanoparticles designed to improve the survival of brain tumor patients by increasing surgical efficiency and mediating adjuvant photodynamic therapy. By optically imaging tumor margins, targeted multifunctional nanoparticles will enable maximal surgical resection, while minimizing adjacent tissue damage. In addition, the same nanoparticles will be used intraoperatively to mediate photodynamic therapy, thereby eradicating occult or un-resectable tumor. This combination presents a unique approach towards a highly significant practical outcome, a large quantitative improvement in the survival statistics of patients with malignant brain cancers. For instance, increases in survival on the order of up to 100% are expected for pediatric low/high grade glioma. Specifically we propose the synthesis of dye-labeled nanoparticles that can be administered intravenously and selectively targeted to brain tumors to optimize the ability of neurosurgeons to delineate neoplasm and healthy nervous tissue. Furthermore, it is proposed that photodynamic components inside the same targeted nanoparticles will enable the eradication of residual tumor following surgical resection. The surgical exposure, performed for resection, will provide a corridor for the efficient delivery of visible laser light to unresectable or occult tumor, for photodynamic therapy. The multifunctional nanoparticles will consist of a biodegradable polyacrylamide core containing blue delineation dye and photosensitizer. 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 with tumor-homing F3 peptide. We demonstrated previously the high therapeutic index, non-toxicity and bio-elimination of similar nanoparticles. The ability of targeted multifunctional nanoparticles to enable intraoperative optical delineation and photodynamic therapy (PDT) will be tested in several animal models of glioma. The proposed research was designed and will be carried out by an existing collaborative team of investigators, including experts in applied physics, bio-nanotechnology, chemistry, neurosurgery, neuropathology, neurotoxicology, optical and MRI imaging, and photodynamic therapy.

描述（由申请人提供）：在过去的三十年中，脑肿瘤治疗的改进对结果几乎没有影响。我们建议开发靶向的多功能纳米颗粒，旨在通过提高手术效率和介导辅助光动力治疗来提高脑肿瘤患者的生存率。通过对肿瘤边缘进行光学成像，靶向多功能纳米颗粒将能够实现最大限度的手术切除，同时最大限度地减少邻近组织的损伤。此外，相同的纳米颗粒将在术中用于介导光动力疗法，从而根除隐匿性或不可切除的肿瘤。这种组合提供了一种独特的方法，可以获得非常显著的实际结果，即恶性脑癌患者生存统计数据的大量改善。例如，对于儿科低/高级别胶质瘤，预期存活率增加高达100%。具体来说，我们提出了染料标记的纳米颗粒，可以静脉注射和选择性地针对脑肿瘤，以优化神经外科医生描绘肿瘤和健康神经组织的能力的合成。此外，提出了相同靶向纳米颗粒内的光动力学组分将使得能够根除手术切除后的残留肿瘤。为切除而进行的手术暴露将为有效地将可见激光输送到不可切除或隐匿的肿瘤提供走廊，以进行光动力治疗。多功能纳米颗粒将由含有蓝色描绘染料和光敏剂的可生物降解的聚丙烯酰胺核心组成。纳米颗粒尺寸（30-70 nm）被设计为允许外渗穿过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血脑屏障的通道。将通过用肿瘤归巢F3肽包被纳米颗粒来优化纳米颗粒在肿瘤部位的定位。我们以前证明了类似纳米颗粒的高治疗指数，无毒和生物消除。靶向多功能纳米颗粒使术中光学描绘和光动力学治疗（PDT）的能力将在几种神经胶质瘤动物模型中进行测试。拟议的研究是由现有的研究人员合作团队设计并进行的，包括应用物理学，生物纳米技术，化学，神经外科，神经病理学，神经毒理学，光学和MRI成像以及光动力疗法的专家。