The major stumbling block in the implementation of oxidoreductase enzymes in continuous processes is their stark dependence on costly cofactors that are insoluble in organic solvents. We describe a chemical strategy that allows producing nanobiocatalysts, based on an oxidoreductase enzyme, that performs biocatalytic reactions in hydrophobic organic solvents without external cofactors. The chemical design relies on the use of a silica-based carrier nanoparticle, of which the porosity can be exploited to create an aqueous reservoir containing the cofactor. The nanoparticle core, possessing radial-centred pore channels, serves as a cofactor reservoir. It is further covered with a layer of reduced porosity. This layer serves as a support for the immobilisation of the selected enzyme yet allowing the diffusion of the cofactor from the nanoparticle core. The immobilised enzyme is, in turn, shielded by an organosilica layer of controlled thickness fully covering the enzyme. Such produced nanobiocatalysts are shown to catalyse the reduction of a series of relevant ketones into the corresponding secondary alcohols, also in a continuous flow fashion.