Distribution of Particles in Human Stem Cell-Derived 3D Neuronal Cell Models: Effect of Particle Size, Charge, and Density

• Published in: Biomacromolecules 2020-08, Vol.21 (8), p.3186-3196
• Main Authors: Czuba-Wojnilowicz, Ewa, Miellet, Sara, Glab, Agata, Viventi, Serena, Cavalieri, Francesca, Cortez-Jugo, Christina, Dottori, Mirella, Caruso, Frank
• Format: Article
• Language: English
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/acs.biomac.0c00626

Neurodegenerative diseases are generally characterized by a progressive loss of neuronal subpopulations, with no available cure to date. One of the main reasons for the limited clinical outcomes of new drug formulations is the lack of appropriate in vitro human cell models for research and validation. Stem cell technologies provide an opportunity to address this challenge by using patient-derived cells as a platform to test various drug formulations, including particle-based drug carriers. The therapeutic efficacy of drug delivery systems relies on efficient cellular uptake of the carrier and can be dependent on its size, shape, and surface chemistry. Although considerable efforts have been made to understand the effects of the physiochemical properties of particles on two-dimensional cell culture models, little is known of their effect in three-dimensional (3D) cell models of neurodegenerative diseases. Herein, we investigated the role of particle size (235–1000 nm), charge (cationic and anionic), and density (1.05 and 1.8 g cm–3) on the interactions of particles with human embryonic stem cell-derived 3D cell cultures of sensory neurons, called sensory neurospheres (sNSP). Templated layer-by-layer particles, with silica or polystyrene cores, and self-assembled glycogen/DNA polyplexes were used. Particles with sizes