Available treatments for brain disorders are commonly pharmacological in nature. Yet, the efficacy and the risk/benefit ratio of brain therapeutics -when they exist- are often dampened by the selectivity of the blood-brain barrier and off-target actions of the molecules, at the periphery as well as in the brain. To improve the efficacy of therapeutic molecules for the brain, their loading in polymersomes (synthetic polymer vesicles) represents a promising strategy due to their high stability, versatility and ability to transport drugs with high efficiency. However, encapsulation does not allow to precisely control time and space of drug release, limiting therapeutic applications. In parallel, neuroscience research has shown an impressive development with light-based technologies to control and record brain circuits (e.g. optogenetics, fiber photometry, etc.). However, these developments do not allow to release bioactive molecules in brain tissue. Here, we combined encapsulation and photostimulation principles, in order to release molecules in the brain with high spatial and temporal control. Following the work done by the project partners, we formulated polymersomes loaded with new photocleavable dyes. Characterization of polymersomes with confocal microscopy showed that their mean diameter is around 8 µm. The time of irradiation for the rupture of polymersome’s at specific wavelength was quantified in solution and in a gel environment mimicking brain tissue. Furthermore, biosafety of polymersomes was assessed in vitro and in vivo for up to three weeks. This work established the potential of biocompatible photoactivable polymersomes for the delivery of bioactive molecules to the brain in vivo.