Nanobiophotonics Enabled Tumor Surgery and Intraoperative PDT

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，对于儿童和成人的脑肿瘤，已知通过放射学完全手术切除可以最大限度地提高生存率。不幸的是，即使采用最好的显微外科技术，切除后也可能留下残留的mri可证实的肿瘤。纳米粒子辅助神经外科，或应用纳米技术来增强神经外科技术，在这里被提出，以最大限度地提高手术效率，通过可见描绘肿瘤组织和介导辅助光动力治疗。多功能肿瘤靶向纳米平台（TNP）将用于描绘肿瘤，从而实现最大程度的手术切除，同时最大限度地减少邻近组织损伤。此外，同样的多功能纳米颗粒将在术中用于介导光动力治疗，以消除隐匿或不可切除的肿瘤。在切除过程中产生的手术暴露将为光动力治疗所需的可见光的有效输送提供通道。TNP将由一个缓慢可生物降解的聚丙烯酰胺核心组成，其中含有光学染料和光敏剂分子。纳米颗粒的大小被设计成允许通过肿瘤内血脑屏障破裂的区域外渗，同时最小化穿过完整血脑屏障的通道。在纳米颗粒表面包裹肿瘤归巢肽F3，可优化纳米颗粒在肿瘤部位的定位。先前的研究表明，高治疗指数和令人满意的生物消除类似的纳米颗粒能够使PDT，而不会对邻近的神经组织造成附带损伤。多功能纳米颗粒术中光学描绘和光动力治疗（PDT）的能力将首先在体外开发，随后将在几种胶质瘤动物模型中进行临床前应用。总之，本提案通过扩展我们实验室先前开发的生物光子纳米器件的能力，引入了一种新的脑肿瘤治疗方法。重要的是，拟议的研究将由具有从生物物理学到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.