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.
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