Cellular Activity Modulation Mediated by Near Infrared-Irradiated Polydopamine Nanoparticles: In Vitro and Ex Vivo Investigation

The precise control of cell activity is crucial for understanding and potentially treating many disorders. Focusing on neurons and myotubes, recent advancements in nanotechnology have introduced photoresponsive nanoparticles as an alternative tool for modulating cell function with high spatial and temporal resolution. This approach offers a noninvasive alternative to traditional stimulation techniques, reducing potential tissue damage and improving the specificity of cell activation. Here, we introduce an approach envisioning fully organic polydopamine nanoparticles (PDNPs) to remotely modulate the activity of differentiated SH-SY5Y cells and differentiated C2C12 cells, via near-infrared (NIR) laser stimulation. Confocal microscopy imaging revealed the possibility of thermally activating individual neuron-like cells, eliciting a significant cellular response characterized by the generation of calcium transients and the subsequent release of the neurotransmitter acetylcholine. Similarly, we demonstrated the possibility of precisely triggering the muscle contraction of single myotubes. Additionally, we investigated the antioxidant properties of PDNPs, demonstrating their capacity to prevent an increase in oxidative stress levels related to an increase in intracellular temperature. Moreover, proteomic analysis revealed that a PDNP treatment could positively affect neuronal plasticity and nervous system maturation, besides promoting muscle growth and preserving its functional integrity, underscoring its potential to support both neural and musculoskeletal development. Eventually, the effect of the NIR laser irradiation in the presence of PDNPs in neuron-like cells was successfully evaluated ex vivo on brains of <i>Drosophila melanogaster</i>, genetically modified to express the fluorescent calcium indicator jGCaMP7c.