CamoUflaged nanopaRticle-driven duAl Therapy to eradicate aggressIVe nEuroblastoma

forthcoming

Neuroblastoma (NB) is a highly aggressive paediatric cancer, accounting for 15% of childhood cancer deaths. The 5-year survival rate for high-risk NB patients is less than 50%. Despite the significant advances in treatment options, the high tumour heterogeneity, drug resistance, and severe toxicities associated with conventional therapies continue to result in poor outcomes for high-risk NB patients. Recent studies showed that these challenges, along with frequent relapses, may be linked to the intrinsic resistance of a specific population of cells known as cancer stem cells (CSCs). CURATIVE aims to address this by developing a chitosan-based nanoparticle (NP) that co-encapsulates a systematically identified and optimized synergistic combination of drugs designed to target both CSCs and a key mechanism driving NB progression. The NP, which will enable controlled and sustained drug release, will be coated with plasma membranes derived from NB cells to enhance tumour targeting and accumulation through homotypic targeting. By leveraging the innovative use of NB cell membranes, the NP can closely mimic the tumour environment, allowing it to evade the immune system and preferentially accumulate at the tumour site. This approach enhances both specificity and efficacy, while simultaneously reducing off-target effects and minimizing systemic toxicity. The expected outcomes of CURATIVE include increased survival and treatment efficacy, reduced relapse rates and toxicity, and improved quality of life for paediatric patients. Overall, CURATIVE is positioned to provide valuable insights and resources to the scientific community, supporting the EU's objectives of advancing innovation in paediatric cancer care.