Nanobiophotonics Enabled Tumor Surgery and Intraoperative PDT

纳米生物光子学支持肿瘤手术和术中 PDT

基本信息

批准号：
7914680
负责人：
Raoul Kopelman
金额：
$ 33.56万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7914680
关键词：
Address Adjuvant Adjuvant Chemotherapy Adjuvant Therapy Adult Adverse effects Affect Animal Model Area Biophotonics Biophysics Blood - brain barrier anatomy Brain Neoplasms Buffaloes Cell Line Chemistry Childhood Contrast Media Development Dose Dyes Evaluation Excision Extravasation FDA approved Glioma Goals Hospitals Human Image In Vitro Institutes Isosulfan Blue Laboratories Lasers Left Light Magnetic Resonance Imaging Malignant Neoplasms Mediating Methodology Methods Michigan Microscopic Modeling Modification Molecular Nanotechnology Nerve Tissue Neurosurgeon Normal tissue morphology Operative Surgical Procedures Optics Outcome Patients Peptides Pharmacologic Substance Phase Photochemotherapy Photosensitizing Agents Phototoxicity Porfimer Sodium Protocols documentation Radiation Radiation Oncology Rattus Refractory Reporting Research Research Personnel Residual Tumors Residual state Site Staining method Stains Techniques Testing Therapeutic Therapeutic Index Time Tissues Tumor Debulking Universities Unresectable Visible Radiation Visual Work base clinically relevant design gliosarcoma improved in vivo interdisciplinary approach iron oxide molecular imaging multidisciplinary nanodevice nanoparticle neoplastic neurosurgery neurotoxicology novel novel strategies nucleolin oncology polyacrylamide pre-clinical relating to nervous system research study success tumor

项目摘要

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，脑肿瘤治疗的改善对结果的影响很小。尽管如此，已知小儿和成人脑肿瘤的生存均通过射线照相完整的手术切除最大化。不幸的是，即使采用了最佳的显微外科技术，切除也可能留下残留的MRI可示威肿瘤。纳米颗粒的辅助神经外科或纳米技术在这里提出了纳米技术来增强神经外科技术，以通过明显地描述肿瘤组织并介导辅助光学疗法来最大程度地提高手术效率。多功能肿瘤靶向纳米板（TNP）将用于描绘肿瘤，从而实现最大的手术切除，同时最大程度地减少相邻的组织损伤。另外，术中将使用相同的多功能纳米颗粒来介导光动力疗法以消除神秘或无法切除的肿瘤。在切除过程中产生的手术暴露将为有效传递光动力疗法所需的可见光提供走廊。 TNP将由含有光敏染料和光敏剂分子的可缓慢生物降解的聚丙烯酰胺芯组成。纳米颗粒的大小旨在使肿瘤内血脑屏障分解区域进行渗出，同时最大程度地减少对完整的血脑屏障的传递。纳米颗粒在肿瘤部位的定位将通过将纳米颗粒涂上肿瘤为肿瘤的F3肽来优化。先前的工作表明，类似的纳米颗粒具有高度治疗指数和令人满意的生物灭绝，能够启用PDT而不会对相邻神经组织造成副作用。多功能纳米颗粒能够最初在体外开发术中光学描述和光动力疗法（PDT）的能力，随后将在几种神经胶质瘤动物模型中进行临床前使用。总而言之，该提案通过扩展了以前在我们的实验室中开发的生物光电纳米驱动器的能力，引入了一种新颖的脑瘤治疗方法。重要的是，拟议的研究将由一群不同的研究人员进行，其专业知识从生物物理学到神经外科肿瘤学。最终目标是将纳米技术的进步应用于脑肿瘤的手术和辅助治疗中的挑战。