Here, we describe the design of a novel particle-to-particle intercommunicated nanosystem for dual delivery, triggered by physical and chemical inputs. The nanosystem was composed of an Au-mesoporous silica Janus nanoparticle loaded with paracetamol, mechanized with light-sensitive supramolecular gates at the mesoporous face and functionalized on the metal surface with the enzyme acetylcholinesterase. The second component was a mesoporous silica nanoparticle loaded with rhodamine B and gated with thiol-sensitive ensembles. Upon irradiation of this nanosystem with a near-UV light laser, an analgesic drug was released from the Janus nanomachine due to disassembling of the photosensitive gating mechanism. Further addition of N-acetylthiocholine leads to the enzymatic production of thiocholine at the Janus nanomachine, thus acting as a "chemical messenger" causing the disruption of the gating mechanism at the second mesoporous silica nanoparticle with the subsequent dye release.