Real-time monitor of drug-release from drug formulations in a noninvasive way can provide spatio-temporal information for drug activation and guide further clinical rational administration. In this work, a molecular shuttle, as a typical nanosized artificial molecular machine, was managed to act as a conceptually-new nanotheranostics for oxaliplatin. A post-recognition strategy was utilized, where a default supramolecular-dye couple was pre-blocked. The rational design, synthesis, characterization and proof-of-concept of this strategy were described in detail. The drug-release upon reducing environment can be translated into near-infrared (NIR) fluorescence signal (OFF-to-ON), allowing to track the drug-release procedure by multi-modal images including IVIS, FLECT and photoacoustic imaging. The versatile nanotheranostics system can target to triple negative breast tumor via conjugated F3 peptide, and show an improved anti-tumor efficacy with much lower side effect. The intelligent nanotheranostics system based on molecular shuttle provides new reference for precision medicine in preclinical trial and postclinical evaluation. Copyright © 2019. Published by Elsevier Ltd.