title: Controlling the neuronal differentiation of stem cells by the intracellular delivery of retinoic acid-loaded nanoparticles.
abstract: The manipulation of endogenous stem cell populations from the subventricular zone (SVZ), a neurogenic niche, creates an opportunity to induce neurogenesis and influence brain regenerative capacities in the adult brain. Herein, we demonstrate the ability of polyelectrolyte nanoparticles to induce neurogenesis exclusively after being internalized by SVZ stem cells. The nanoparticles are not cytotoxic for concentrations equal or below 10 μg/mL. The internalization process is rapid, and nanoparticles escape endosomal fate in a few hours. Retinoic acid-loaded nanoparticles increase the number of neuronal nuclear protein (NeuN)-positive neurons and functional neurons responding to depolarization with KCl and expressing NMDA receptor subunit type 1 (NR1). These nanoparticles offer an opportunity for in vivo delivery of proneurogenic factors and neurodegenerative disease treatment.
authors.affiliation: Chemical Engineering Department, University of Coimbra, Pinhal de Marrocos, 3030-290 Coimbra, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Maia
authors.forename: Tiago
authors.initials: T
authors.lastname: Santos
authors.forename: Sezin
authors.initials: S
authors.lastname: Aday
authors.forename: Fabienne
authors.initials: F
authors.lastname: Agasse
authors.forename: Luísa
authors.initials: L
authors.lastname: Cortes
authors.forename: João O
authors.initials: JO
authors.lastname: Malva
authors.forename: Liliana
authors.initials: L
authors.lastname: Bernardino
authors.forename: Lino
authors.initials: L
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D001692:Biological Transport; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000378:metabolism* / Q000633:toxicity; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D053758:Nanoparticles / Q000633:toxicity; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D004337:Drug Carriers; D014212:Tretinoin