Optical Switchers to Manipulate Intracellular Pathways and Boost Tissue Regeneration

The possibility to remotely manipulate intracellular pathways in single cells is among the current goals of regenerative medicine, demanding new strategies to enhance tissue repair and reprogram stem cell activity. Plasmonic nanomaterials are addressing this need, due to improvements in the controlled synthesis allowing convenient regulation and precise thermal positioning. Leveraging on the thermal properties of gold nanoprisms (AuNPs) and on the unparalleled regenerating capabilities of the small invertebrate Hydra vulgaris, here the possibility to activate the molecular machinery underlying the animal regeneration by using AuNPs and applying regular pulses of near infrared irradiation (NIR) is shown. The efficiency of the head regeneration, reproductive capability, and stem cell proliferation rate are boosted by the AuNP photostimulation, indicating NIR triggered hyperthermia as new tool to enhance tissue regeneration. By transcriptional profiling of key developmental genes in animals exposed to external heat or irradiated an estimation of the heat developed in vivo by intracellular nanoheaters is obtained, revealing Hydra as a living thermometer to test performance of plasmonic materials. These results shed light on a novel function of heat emitting nanoparticles to control cell stemness through the activation of molecular pathways that can be targeted for regenerative medicine or wound healing strategies. Gold nanoprisms act as optical switchers inside the tissue of Hydra vulgaris. Following NIR illumination the heat locally delivered modulates several molecular pathways, promoting stem cell self‐renewal, proliferation and differentiation of head tissue. The final outcome is the enhancement of the regeneration efficiency.