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Developing smart Coordination Polymer Nanoparticles as Biomedicine for Metastatic Neuroblastoma
(NanoCPPs)
Date du début: 16 févr. 2015,
Date de fin: 15 févr. 2017
PROJET
TERMINÉ
Metastatic neuroblastoma is one of the most challenging malignancies of childhood, being associated with the highest death rate in pediatric oncology (20%). Moreover its prognosis is very poor, practically incurable, what shows the inability of nowadays chemotherapy to eradicate all the illness, underlining the need for novel therapeutic approaches. A current study of the European Group for study of the Neuroblastoma has shown profits in the survival of patients by means of the combination of several drugs (protocol COJEC: vincristine, carboplatin, etoposide and ciclofosfamide). However, such treatment shows a very important deep medullary aplasia as a secondary effect.Our hypothesis is that encapsulation of the NB drug cocktail can significantly improve nowadays disease treatment in such: I) will protect drugs from degradation before reaching cancer cells, II) will ensure their simultaneous actuation and III) last but not least, it will allow us to minimize undesirable medullary aplasia side effects upon specific vectorization of the drug cocktail to the target cells with targeting agents able to address GD2, a glycolipid highly expressed on the cell surface of neuroblastoma.Such exigent specifications require a unique multifunctional system that not all the reported drug carriers can achieve. Our choice is a new family of coordination polymer (CP) nanoparticles rrecently used with this aim by the host group due to their advantages: I) can encapsulate multiple active principles with high yield within the same particle, II) the presence of biocompatible metal ions can add additional fluorescence properties that allow us to follow the cell internalization and biodistribution, III) nanoparticles can be functionalized with specific targeting biomolecules and IV) preliminary in vitro cytotoxicity assays already showed that the encapsulated drugs could be effectively used to induce the cell death.
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