Nanobiophotonics Enabled Tumor Surgery and Intraoperative PDT

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。纳米颗粒辅助神经外科，或应用纳米技术来提高神经外科技术，通过直观地描绘肿瘤组织和介导辅助光动力疗法来最大化手术效率。多功能肿瘤靶向纳米平台(TNP)将被用来描绘肿瘤，从而实现最大限度的手术切除，同时将邻近组织的损伤降至最低。此外，同样的多功能纳米颗粒将在术中用于介导光动力疗法，以消除隐匿性或无法切除的肿瘤。在切除过程中产生的手术暴露将为光动力疗法所需的可见光的有效传递提供一条走廊。TNP将由一个可缓慢生物降解的含有光学染料和光敏剂分子的聚丙烯酰胺核心组成。这种纳米颗粒的大小被设计成允许渗出穿过肿瘤内血脑屏障破坏的区域，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将肿瘤归巢F3肽包裹在纳米粒子上而优化。以前的工作表明，类似的纳米粒子具有较高的治疗指数和令人满意的生物消除能力，能够在不对邻近神经组织造成附带损害的情况下进行PDT。多功能纳米粒子能够实现术中光学描绘和光动力学治疗(PDT)的能力将首先在体外开发，稍后将改进用于几种胶质瘤动物模型的临床前使用。总而言之，这项建议引入了一种新的脑肿瘤治疗方法，通过扩展我们实验室以前开发的生物光子学纳米设备的能力。重要的是，拟议的研究将由一组具有从生物物理学到神经外科肿瘤学的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解决脑肿瘤手术和辅助治疗中的挑战。

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.