The overall goal of this project is to develop a much more efficacious treatment method for glioblastoma (GBM) with significantly reduced side effects. GBM is the most common and most aggressive primary brain tumor. Currently, standard treatment of GBM is based on surgery (if feasible) followed by radiotherapy and chemotherapy. However, because very invasive GBM tumors have finger-like projections into healthy areas, making it impossible to completely remove the tumor by surgery and/or radiotherapy, and the blood-brain barrier prevents chemicals from crossing into the brain, making it difficult to treat the tumor using chemotherapy, the harsh reality for GBM patients is that there is no effe...

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The overall goal of this project is to develop a much more efficacious treatment method for glioblastoma (GBM) with significantly reduced side effects. GBM is the most common and most aggressive primary brain tumor. Currently, standard treatment of GBM is based on surgery (if feasible) followed by radiotherapy and chemotherapy. However, because very invasive GBM tumors have finger-like projections into healthy areas, making it impossible to completely remove the tumor by surgery and/or radiotherapy, and the blood-brain barrier prevents chemicals from crossing into the brain, making it difficult to treat the tumor using chemotherapy, the harsh reality for GBM patients is that there is no effective therapy and a dim prognosis with a median survival time of only 15 months and a 5 year survival of less than 5%. Recently, we have fabricated unique radioactive nanoparticles, which is termed as nanoseeds, and composed of 3 nanometer gold nanoparticles decorated with radioactive isotopes. Here, we propose to use this nano-size radiation source to treat GBM. Nanoseeds will first be conjugated with biomolecules specifically targeting tumor blood vessel, so that after intravenous injection nanoseeds can reach and retain in the blood vessel of GBM tumor. The radiation from the nanoseeds in blood vessel can reach and kill cancer cells inside the tumor, but is still mostly confined in tumor volume without spreading into normal brain tissue. The nanoseeds do not need to cross the blood-brain barrier to achieve therapeutic effect. Meanwhile, the finger-like projections from the tumor are also well vascularized, so the nanoseeds can reach to entire tumor volume including these projections. Because of their ultra small size, nanoseeds entered into circulation system can eventually be excreted into urine with a minimal uptaking in other organs, avoiding systemic toxicity. If successful, this new therapy would offer GBM patients with longer survival and better quality of life.

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