Polymeric Nanoparticles to Control the Differentiation of Neural Stem Cells in the Subventricular Zone of the Brain

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.

MicroRNA-124 loaded nanoparticles enhance brain repair in Parkinson's disease

“…microRNAs) [6][7][8][9] regulate the neurogenic niche. MicroRNAs (miR) are able to regulate hundreds of genes [10] at the posttranscriptional level by inhibiting mRNA translation or inducing mRNA degradation [11].…”

Blue light potentiates neurogenesis induced by retinoic acid-loaded responsive nanoparticles

“…On the other hand, proliferating astrocytes (GFAP+/Ki67+) decreased in a similar fashion when treated with either 60 sec of laser or the combination of LR-NP+60s. We have previously reported that RA-loaded polymeric nanoparticles do not affect NSC astrocytic differentiation [39], as such, this new result might indicate that decreased astrocytic proliferation is a characteristic restricted to laser-induced differentiation.…”

Nanomedicine Approaches to Modulate Neural Stem Cells in Brain Repair

“…Importantly, functionalized nanostructured hydrogels were shown to successfully induce NSC differentiation while supporting tissue regeneration [6]. Recently, we have successfully developed a NP formulation capable of controlling NSC differentiation both in vitro and in vivo [3,4]. Contrary to soluble retinoic acid (RA), our results demonstrated that RA-NPs injected intracerebroventricularly contributed to the successful neuronal commitment of mouse subventricular zone (SVZ) NSCs.…”

“…Nanoparticulate systems for brain delivery (e.g., anticancer drugs, analgesics, antiAlzheimer's and anti-Parkinson's drugs) have been described in the past 25 years [2]. However, modulation of the activity/ differentiation of NSCs by nanoparticulate systems releasing small molecules was only recently demonstrated [3,4]. Current progress in the nanomedicine field has been stimulated by better understanding the biology of NSCs and by identifying molecular players capable of modulating their activity, proliferation, migration, and differentiation.…”