Aptamers, oligonucleotides evolved to be specific against a target ligand, are promising as selective drug delivery agents for cancer cells that express unique biomarkers on their surfaces. However, cell surface antigens do not always differentiate among cells as specifically as desired. The altered metabolism of cancer cells results in pronounced changes to their microenvironment, particularly through altered metabolite concentrations. In this study these metabolite markers of tumor cells are leveraged to rationally engineer a two-stage aptamer nanomachine, in which activates the aptamer cell binding domain is activated only once its metabolite domain has been bound. This nanomachine recognizes ATP as its metabolite, and binds to T Cells when activated. For this reason, I termed the aptamer ART, for A​TP-​R​egulated ​T​1C. We demonstrate that aptamer binding activity is controllable by the conformational status of an intramolecular domain via helix destabilization. Furthermore, it is shown that cancer indicative metabolites can be used to regulate binding of this nanomachine to cancerous T Leukocytes. In this way, we have developed a new platform for specific cancer recognition and drug delivery, which relies not only on cell-specific antigens but also on the conditions surrounding the cells. This technology will enable higher dosages of chemotherapeutic agents to be used with reduced side effects to healthy cells, enabling a safer and more effective form of chemotherapy.