Nanobiophotonics Enabled Tumor Surgery and Intraoperative PDT

纳米生物光子学支持肿瘤手术和术中 PDT

• 批准号: 7665205
• 负责人: Raoul Kopelman
• 金额: $ 37.97万
• 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: 2007-08-27 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7665205
• 关键词: Address; Adjuvant; Adjuvant Therapy; Adult; Animal Model; Area; Biophotonics; Biophysics; Blood - brain barrier anatomy; Brain Neoplasms; Childhood; Dyes; Excision; Extravasation; Glioma; Goals; In Vitro; Laboratories; Left; Mediating; Nanotechnology; Operative Surgical Procedures; Optics; Outcome; Peptides; Photochemotherapy; Photosensitizing Agents; Range; Research; Research Personnel; Residual state; Site; Techniques; Therapeutic Index; Tissues; Unresectable; Visible Radiation; Work; design; nanodevice; nanoparticle; neoplastic; neurosurgery; novel strategies; oncology; polyacrylamide; pre-clinical; relating to nervous system; 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. Nanoparticle assisted neurosurgery, or the application of nanotechnology to enhance neurosurgical technique, is proposed here to maximize surgical efficiency by visibly delineating neoplastic tissue and mediating adjuvant photodynamic therapy. Multifunctional tumor targeted nanoplatform (TNP) will be used to delineate tumor, thus enabling maximal surgical resection, while minimizing adjacent tissue damage. In addition, the same multifunctional nanoparticles will be used intraoperatively to mediate photodynamic therapy to eliminate occult or unresectable tumor. The surgical exposure, created during resection, will provide a corridor for the efficient delivery of visible light necessary for photodynamic therapy. The TNP will consist of a slowly biodegradable polyacrylamide core containing optical dye and photosensitizer molecules. The nanoparticle size has been designed to allow extravasation across the areas of blood brain barrier breakdown within tumors, while minimizing passage across an intact blood-brain barrier. The localization of nanoparticles at tumor sites will be optimized by coating the nanoparticles with tumor-homing F3 peptide. Previous work demonstrated the high therapeutic index and satisfactory bio-elimination of similar nanoparticles capable of enabling PDT without causing collateral damage to adjacent neural tissue. The ability of multifunctional nanoparticles to enable intraoperative optical delineation and photodynamic therapy (PDT) will be initially developed in vitro and will later be refined for preclinical use in several animal models of glioma. In summary, this proposal introduces a novel approach to brain tumor therapy, through an extension of the capabilities of biophotonic nano-devices previously developed in our laboratories. Importantly, the proposed research will be carried out by a diverse group of investigators with expertise ranging from biophysics to neurosurgical oncology. The ultimate goal is to apply advances in nanotechnology to address the challenges in the surgical and adjuvant therapy of brain tumors.

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。尽管如此，通过放射学完全手术切除，儿童和成人脑肿瘤的生存率被认为是最大化的。不幸的是，即使使用最好的显微外科技术，切除可能会留下残留的，MRI可证实的肿瘤。纳米粒子辅助神经外科手术，或纳米技术的应用，以提高神经外科技术，提出了在这里，以最大限度地提高手术效率，可见划定肿瘤组织和介导的辅助光动力治疗。多功能肿瘤靶向纳米平台（TNP）将用于描绘肿瘤，从而实现最大限度的手术切除，同时最大限度地减少相邻组织的损伤。此外，相同的多功能纳米颗粒将在术中用于介导光动力学治疗，以消除隐匿性或不可切除的肿瘤。在切除过程中产生的手术曝光将为光动力治疗所需的可见光的有效输送提供走廊。TNP将由含有光学染料和光敏剂分子的缓慢生物降解的聚丙烯酰胺核心组成。纳米颗粒的大小被设计为允许外渗穿过肿瘤内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。先前的工作证明了类似纳米颗粒的高治疗指数和令人满意的生物消除，能够实现PDT而不对邻近神经组织造成附带损伤。多功能纳米颗粒使术中光学描绘和光动力学治疗（PDT）的能力最初将在体外开发，随后将在几种神经胶质瘤动物模型中进行临床前应用。总之，该提案通过扩展我们实验室先前开发的生物光子纳米设备的能力，引入了一种新的脑肿瘤治疗方法。重要的是，拟议的研究将由一组具有生物物理学和神经外科肿瘤学等专业知识的不同研究人员进行。最终目标是应用纳米技术的进步来应对脑肿瘤手术和辅助治疗的挑战。