Controlling the neuronal differentiation of stem cells by the intracellular delivery of retinoic acid-loaded nanoparticles

ACS Nano. 2011 Jan 25;5(1):97-106. doi: 10.1021/nn101724r. Epub 2010 Dec 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Carriers / metabolism*
  • Drug Carriers / toxicity
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism*
  • Mice
  • Nanoparticles* / toxicity
  • Neurons / cytology*
  • Neurons / drug effects
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Tretinoin / metabolism
  • Tretinoin / pharmacology*

Substances

  • Drug Carriers
  • Tretinoin