Control of Wnt/β-Catenin Signaling Pathway in Vivo via Light Responsive Capsules

The possibility to remotely manipulate intracellular pathways in single cells is among the current goals of biomedicine, demanding new strategies to control cell function and reprogramming cell fate upon external triggering. Optogenetics is one approach in this direction, allowing specific cell stimulation by external illumination. Here, we developed optical switchers of an ancient and highly conserved system controlling a variety of developmental and adult processes in all metazoans, from Hydra to mammals, the Wnt/beta-catenin signaling pathway. An intracellular modulator of the Wnt pathway was enclosed into polyelectrolyte multilayer microcapsules engineered to include self-tracking (i.e., fluorescence labeling) and light mediated heating functionalities (i.e., plasmonic nanoparticles). Capsules were delivered in vivo to Hydra and NIR triggered drug release caused forced activation of the Wnt pathway. The possibility to remotely manipulate the Wnt pathway by optical switchers may be broadly translated to achieve spatiotemporal control of cell fate for new therapeutic strategies.