Abstract
Neuroblastoma is the most common solid tumor outside the brain of infants and very young children. A substantial part of neuroblastoma patients presents with high-risk neuroblastoma disease. In fact, these children have a poor prognosis, do not respond to therapy or even relapse. Therefore, there is an urgent need to find novel treatment strategies. Recently, our research group discovered a new approach to kill aggressive therapy-resistant neuroblastoma cells in mice by inducing a sort of biological rusting in cancer cells, called ferroptosis. Ferroptosis is a type of cell death that rusts away the cellular membrane, which quickly kills the cells. By using nanoparticles, the lab was able to minimize side effects of treatment and enhance tumor targeting. However, to get full tumor regression without relapse using a nanomedicinal approach, it is needed to further improve the efficacy of targeting ferroptosis in neuroblastoma. The aim of this project is to recondition high-risk neuroblastoma to a ferroptosis sensitive state, by acting on anti-ferroptosis mechanisms in cancer cells. In addition, ferroptosis-sensitizing compounds will be encapsulated in lipid nanoparticles, currently used for the Covid-19 RNA vaccines. These ferroptosis-sensitizing nanomedicines will be tested and validated in cell- and patient-derived high-risk neuroblastoma mouse models and provide a steppingstone to clinical investigation of ferroptosis targeting as anti-cancer therapy.
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