Cancer remains a significant challenge in the medical field (Siegel et al., 2012). Conventional treatments frequently have serious side effects that lower patients' quality of life and cannot totally eradicate the disease (Hendijani, 2015). Additionally, neural progenitor cells might be adversely affected by chemotherapeutic drugs, extinguishing any possibility of nervous tissue regeneration (Dietrich et al., 2006). This emphasizes the importance of precisely targeting cancer cells while preserving healthy brain cells. This work aims at addressing this challenge through the development of polymeric nanoparticles (NPs), which allow crossing the blood-brain barrier (BBB) and protecting neural stem cells. NPs were realized using nanoprecipitation of poly(lactic-co-glycolic acid) (PLGA), and their size, mechanical characteristics, surface charge, and homogeneity were thoroughly characterized. Moreover, their biocompatibility was evaluated with primary murine cortical and hippocampal in vitro cell cultures by means of MTT cell viability assays and electrophysiological recordings on Micro-Electrode Arrays (MEAs). To improve the NPs’ ability of neuronal targeting and internalization, these processes were repeated before and after specific functionalization aimed at optimizing the nanocomposites’ ability of recognizing neuronal progenitor cells. The achieved results suggest that the developed PLGA nanoparticles are stable over time and biocompatible, confirming their safety within the central nervous system: their sizes of 190±5 nm enable them to cross the BBB, and with the appropriate coating, to recognize neural progenitor cells selectively. Moreover, the NPs have the capability to be internalized by them without significantly affecting their metabolic and electrophysiological activity.