Multifunctional Nanomaterials for the Prevention of Radiotherapy's Side Effects and Childhood Cancers
Each year, hundreds of children undergo radiation therapy, in order to treat their primary cancer. Due to radiation's potency and in the absence of highly effective protection systems, these children may suffer brain damage and experience developmental problems. Also, radiation can affect their skin and bone marrow, causing skin cancer and leukemia.
In the US, each year 2,000 children are diagnosed with leukemia and 600 with skin cancer, where many of them have been previously treated with radiation therapy. Therefore, developing new platforms that can protect children from radiation is critical, allowing physicians to minimize radiation's effect on healthy organs. Cerium oxide nanoparticles can protect from ionizing radiation, and serve as sensors of high levels of radiation. We previously demonstrated that these nanoparticles could protect healthy cells from radiation's toxic products, such as reactive oxygen species (ROS). Additionally, we recently developed an implantable device that can sense high levels of ROS, allowing physicians to monitor them with MRI and fluorescence readers.
Based on this previous knowledge, we will develop cerium oxide nanoparticles that can be embedded in adhesive bandages and fabric, in order to protect during radiation therapy and exposure to sun's UV light. Apart from protecting the skin and healthy organs, these systems will be engineered to quickly report high dosages of radiation via MRI and fluorescence. By harnessing nanoparticles' sensitivity and radiation-protective capabilities, we believe that radiotherapy's side effects will be minimized and lower the cases of pediatric cancer.
2016 Project Update
During the second year of our project, we determined that dextran-coated cerium oxide nanoparticles have the ability to selectively protect the body from radiation, by scavenging the harmful products of ionizing radiation, including the extremely toxic reactive oxygen species. Cell-culture and animal studies demonstrated that the nanoparticles prevent inflammation, allowing the body to safely recover after radiation therapy while the tumor shrinks. We also found that reactive oxygen species can kill leukemia in animals that were treated with the iron-containing nanoparticle Feraheme. Since Feraheme is used in the clinic for the treatment of anemia, we believe that this nanoparticle might be an attractive alternative to treat leukemias in pediatric patients, because the nanoparticle selectively kills only the leukemic cells leaving the rest of the body unaffected. Since the most common way to treat cancer patiens is surgery, we designed polymeric nanoparticles that identify lymph nodes, which may harbor cancer cells that can drive metastasis to other organs. Oncologists can use these nanoparticles and the imaging technique Positron Emission Tomography that is common in the clinic to find where these lymph nodes are in the body, and during surgery use the nanoparticles' optical signal to safely remove them, leaving no cancer cell behind. Lastly, we used nanoparticles to home drugs to tumors that expressed a biomarker and image response with MRI, eliminating side effects, improving therapy, enhancing life quality, increasing survival and lowering the costs of cancer treatment.
During the no cost extension period of our project, we focused on identifying new therapeutic approaches for pediatric cancers, which can complement established practices, like surgery and radiation therapy. Specifically, we developed drug delivery carriers that were constructed from compounds that are already used in the clinic. For instance, we created a glucose-based delivery vehicle that could simultaneously deliver two drugs to cancers, achieving tumor regression, preventing drug resistance, and averting disease relapse, without any side effects. Additionally, since immunotherapy is on the rise, we developed imaging agents that allow the tracking of immune cells in the body, using positron emission tomography (PET scan). Importantly, these sensitive probes were made of the clinical iron oxide nanoparticle Feraheme, which was radiolabeled using a creative strategy that preserved the compound, and can be widely used in the clinic. Furthermore, we identified a paradigm-shifting therapeutic that selectively kills cancer cells and has no effect on healthy cells. We anticipate that this new drug will be a promising therapeutic for many pediatric cancers, including glioblastoma, and eliminate side effects, enhance life quality, increase survival and lower the costs of cancer treatment.