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. The Vanden Berghe lab 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. By using nanoparticles, the lab was able to minimize side effects of treatment and enhance tumor targeting. However, to reach full tumor regression without relapse, it is needed to further improve the efficacy of targeting ferroptosis as therapeutic strategy in neuroblastoma. Therefore, we aim to recondition high-risk neuroblastoma cells to a ferroptosis sensitive state, by acting on anti-ferroptosis mechanisms in cancer cells. We successfully developed a sensitizing strategy targeting the lipid composition of the cancer cells using poly-unsaturated fatty acid containing lipid nanoparticles, which are similar to COVID-19 vaccines. Additionally, we identified ferroptosis-sensitizing compounds that act on the cell's lipid metabolism. Recently, we encapsulated such a sensitizing compound in our lipid nanoparticle, resulting in NANOSENSO. This ferroptosis-sensitizing nanomedicine will be tested in cell- and patient-derived high-risk neuroblastoma mouse models as non-toxic pre-treatment to ferroptosis induction. Finally, this would provide a steppingstone to clinical investigation of ferroptosis targeting as anti-cancer therapy.