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Novel nanoparticle-based drug delivery system for neural stem cell targeting and differentiation

Abstract : Neural stem cells (NSCs) are located in specific regions of the central nervous system called niches. Those cells are able to self-renew and to differentiate into specialized neuronal cells (neurons, astrocytes and oligodendrocytes). Due to this differentiation property, NSCs are studied to replace neuronal cells and restore neurological functions in patients affected by neurodegenerative diseases. Several therapeutic approaches have been developed and endogenous NSC stimulation is one of the most promising. Currently, there is no active molecule or therapeutic system targeting endogenous CSNs and inducing their differentiation at the same time. The aim of the work was to provide a drug delivery system able both to target endogenous CSNs and to induce their differentiation in situ. Here, we developed and characterized lipidic nanoparticles (LNC) targeting endogenous NSCs. A peptide called NFL-TBS.40-63, known for its affinity towards NSCs, was adsorbed at the surface of LNC. We observed that NFL-LNC specifically targeted NSC from the brain and not from the spinal cord in vitro and in vivo. To explain this specificity, we characterized and compared NFL-LNC interactions with the plasmatic membrane of both cell types. Finally, we demonstrated that by loading retinoic acid in NFL-LNC we were able to induce brain NSC differentiation in vitro and in vivo. This work contributes to the development of efficient and safe therapies for the treatment of neurodegenerative disease via the differentiation of endogenous NSCs.
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  • HAL Id : tel-02406015, version 1

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Dario Carradori. Novel nanoparticle-based drug delivery system for neural stem cell targeting and differentiation. Human health and pathology. Université d'Angers; Université catholique de Louvain (1970-..), 2017. English. ⟨NNT : 2017ANGE0056⟩. ⟨tel-02406015⟩

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