Rare-earth metal-based nanosystems for facilitating neural stem cell differentiation into neurons and enhancing axonal stability

Overcoming neural injury and facilitating effective repair pose considerable challenges in the field of neural rehabilitation, characterized by extensive disability and limited recovery rates. A critical aspect of reconstructing a functional nervous system revolves around the successful development of operational axons. In our investigation of rare-earth metal-based upconversion nanoparticles (UCNPs), we have discovered their ability to induce the differentiation of PC-12 cells into neurons. Expanding our inquiry into the implications of UCNPs in neural rehabilitation, we have also applied them in primary mouse neurogenesis, resulting in a significant increase in both neural length and quantity. Furthermore, when used during the induction of primary neural stem cells (NSCs), UCNP treatment has shown a dual effect: it enhances the expression of the neuronal marker TUBB3 while simultaneously inhibiting differentiation into astrocytes. This multifaceted impact was sustained in a prolonged neural sphere differentiation experiment, where UCNPs notably enhance the stability of neuronal axons and facilitate the establishment of intercellular connections. In summary, at the cellular level, introducing UCNPs not only promotes neuronal differentiation in NSCs but also sustains axonal growth, stability, and the formation of intercellular connections. These collective findings highlight the significant potential of UCNPs in advancing the frontiers of neural rehabilitation.