Bioorthogonal chemistry provides the possibility to achieve unnatural chemical reactions in living systems without interfering with native bioprocesses. Along the past years, several ligation and click-to-release reactions have been developed enabling to understand or manipulate biological processes through the formation or the breaking of chemical bounds in a stringently controlled fashion. However, the portfolio of reactions that can be undertaken in living systems is yet very small, especially when compared to the wide diversity of chemical transformations that can be conducted in organic solvents. In the NanoChem project, we propose to introduce a new paradigm in the field of bioorthogonal chemistry based on stimuli-responsive bioorthogonal nanoreactors, designed for the ‘on-demand’ synthesis of molecules in living systems. These nanoreactors will be programmed for allowing various chemical transformations in living systems such as coupling reactions, cyclizations, polymerizations, rearrangements and autocatalytic processes. In contrast to previous strategies, the NanoChem technology will allow the formation of chemical bonds that are present in natural products (e.g. urea, amide) without interfering with surrounding biologics. Since such chemistry will take place in a confined space, reaction rates should be considerably accelerated thereby limiting issues associated to the high dilution conditions meet in living systems. Furthermore, the NanoChem technology will offer the possibility to trigger autocatalysis in biological media, leading to signal amplification processes in which one bioorthogonal event will conduct to the activation of multiple bioactive compounds. Thus, this original project in the field of chemistry could lead to potential applications in the domain of human health.