Spatiotemporal control of molecular delivery in the brain using photoactivable polymersomes

Neurological diseases remain a leading cause of disability and mortality, in part because systemically administered therapies poorly access diseased brain regions and lack spatiotemporal control. While innovative nanotechnologies offer stable and versatile carriers for drug delivery, they do not inherently enable localized, on-demand release. In parallel, optical neurotechnologies provide precise control of brain activity but cannot deliver bioactive molecules. Here, we bridge these approaches by developing photoactivatable vesicles based on polymeric amphiphiles (polymersomes) that enable light-triggered, spatially confined release of encapsulated compounds in brain tissue. We assessed their safety in primary cell cultures and in vivo. Through the photorelease of CNQX, a competitive AMPA/kainate receptor antagonist, we demonstrated the stability and precise spatiotemporal control of molecular delivery. This work establishes a platform for optically-guided chemical neuromodulation. Beyond applications in basic and preclinical neuroscience, this strategy opens new avenues for targeted therapies in localized brain disorders, including glioblastoma.