WHO Grade IV Glioma: Glioblastoma multiforme (GBM) is the most common and deadly form of primary brain cancer in adults. The current standard treatment of GBM consists of surgery followed by combined chemo- and radiation therapy (RT); despite this aggressive approach, the median survival time remains just over one year. The primary goal of this research proposal is to therefore develop a novel RadioTheranostic approach to treat GBM that employs for the first time Gold- and SuperParamagnetic Iron Oxide (SPIO)-nanoparticle loaded polymeric Micelles (GSMs) and utilizes Radiation and a Glioma-restricted IL13Ra2-targeting ligand to selectively deliver radiation-enhancing and MR-imagable nanoparticles. With well aligned radiotherapeutic and diagnostic (RadioTheranostic) properties, GSMs will be customized, characterized and modeled for intracranial tumor treatment and imaging. The analyses will include the effects of precisely delivered RT in augmenting spatially targeted GSM accumulation within brain tumors. Leveraging our combined expertise in radiobiology, neuro-oncology, orthotopic and transgenic glioma models, molecular imaging, nanotechnology and bioengineering we will test the central hypothesis that administration of novel GSM formulations will significantly improve the targeting and efficacy of RT for GBM with little to no added toxicity and fulfill the following specific aims Aim 1. Synthesize and characterize GSMs with complementary therapeutic and diagnostic capabilities.
Aim 2. Determine the optimal timing between RT and GSM administration for maximal selective GSM accumulation within intracranial tumors, MR imaging, and RT dose enhancement.
Aim 3. Characterize IL13Ra2-targeted GSMs for imaging and treatment of Glioblastoma. We have marshaled a versatile team with the requisite experience and expertise to successfully test our hypothesis and address our specific aims. These studies together should together help facilitate a breakthrough advance in the treatment of GBM, while helping to fulfill the RadioTheranostic potential of GSMs for this highly intractable and deadly brain tumor.

Public Health Relevance

Glioblastoma multiforme (GBM) is the most common and deadly form of adult primary brain cancer with a current median survival of just over one year. This research focuses on the development and evaluation of an innovative radiation- and receptor- targeted radiotherapeutic and diagnostic ('RadioTheranostic') strategy to improve the efficacy of radiation against these lethal tumors. Results of these studies will ultimately benefit public health by potentially improving therapies against these cancers and brain tumors in general.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Radiation Therapeutics and Biology Study Section (RTB)
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Capala, Jacek
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University of Pennsylvania
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Hajfathalian, Maryam; Amirshaghaghi, Ahmad; Naha, Pratap C et al. (2018) Wulff in a cage gold nanoparticles as contrast agents for computed tomography and photoacoustic imaging. Nanoscale 10:18749-18757
Yan, Lesan; Amirshaghaghi, Ahmad; Huang, Dennis et al. (2018) Protoporphyrin IX (PpIX)-Coated Superparamagnetic Iron Oxide Nanoparticle (SPION) Nanoclusters for Magnetic Resonance Imaging and Photodynamic Therapy. Adv Funct Mater 28:
Amirshaghaghi, Ahmad; Altun, Burcin; Nwe, Kido et al. (2018) Site-Specific Labeling of Cyanine and Porphyrin Dye-Stabilized Nanoemulsions with Affibodies for Cellular Targeting. J Am Chem Soc :
Zeh, Ryan; Sheikh, Saad; Xia, Leilei et al. (2017) The second window ICG technique demonstrates a broad plateau period for near infrared fluorescence tumor contrast in glioblastoma. PLoS One 12:e0182034
Sattiraju, Anirudh; Xiong, Xiaobing; Pandya, Darpan N et al. (2017) Alpha Particle Enhanced Blood Brain/Tumor Barrier Permeabilization in Glioblastomas Using Integrin Alpha-v Beta-3-Targeted Liposomes. Mol Cancer Ther 16:2191-2200
Liu, Jessica F; Yadavali, Sagar; Tsourkas, Andrew et al. (2017) Microfluidic diafiltration-on-chip using an integrated magnetic peristaltic micropump. Lab Chip 17:3796-3803
Thawani, Jayesh P; Amirshaghaghi, Ahmad; Yan, Lesan et al. (2017) Photoacoustic-Guided Surgery with Indocyanine Green-Coated Superparamagnetic Iron Oxide Nanoparticle Clusters. Small 13:
Wang, Hejia Henry; Altun, Burcin; Nwe, Kido et al. (2017) Proximity-Based Sortase-Mediated Ligation. Angew Chem Int Ed Engl 56:5349-5352
Sun, Lova; Joh, Daniel Y; Al-Zaki, Ajlan et al. (2016) Theranostic Application of Mixed Gold and Superparamagnetic Iron Oxide Nanoparticle Micelles in Glioblastoma Multiforme. J Biomed Nanotechnol 12:347-56
Al Zaki, Ajlan; Hui, James Z; Higbee, Elizabeth et al. (2015) Biodistribution, Clearance, and Toxicology of Polymeric Micelles Loaded with 0.9 or 5 nm Gold Nanoparticles. J Biomed Nanotechnol 11:1836-46

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