Polymeric nanoparticles to control the differentiation of neural stem cells in the subventricular zone of the brain

ACS Nano. 2012 Dec 21;6(12):10463-74. doi: 10.1021/nn304541h. Epub 2012 Nov 29.

Abstract

Herein, we report the use of retinoic acid-loaded polymeric nanoparticles as a potent tool to induce the neuronal differentiation of subventricular zone neural stem cells. The intracellular delivery of retinoic acid by the nanoparticles activated nuclear retinoic acid receptors, decreased stemness, and increased proneurogenic gene expression. Importantly, this work reports for the first time a nanoparticle formulation able to modulate in vivo the subventricular zone neurogenic niche. The work further compares the dynamics of initial stages of differentiation between SVZ cells treated with retinoic acid-loaded polymeric nanoparticles and solubilized retinoic acid. The nanoparticle formulation developed here may ultimately offer new perspectives to treat neurodegenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / drug effects
  • Axons / metabolism
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Differentiation* / drug effects
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Drug Carriers / chemistry*
  • Gene Expression Regulation / drug effects
  • Lateral Ventricles / cytology*
  • Mice
  • Nanoparticles / chemistry*
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / metabolism
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Polyethyleneimine / chemistry*
  • Receptors, Retinoic Acid / metabolism
  • Tretinoin / chemistry
  • Tretinoin / metabolism
  • Tretinoin / pharmacology

Substances

  • Ascl1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Drug Carriers
  • Nerve Tissue Proteins
  • Receptors, Retinoic Acid
  • Neurog1 protein, mouse
  • Tretinoin
  • Polyethyleneimine