Drug　administration　customized　to　individual　cells　could　intrinsically　address　cancer　heterogeneity　and　provide　a　safe　and　effective　method　for　delivering　personalized　treatment.　To　accomplish　this,　we　developed　a　smart　nanodrug　delivery　system　characterized　by　cancer　cell-targeted　drug　delivery　and　intracellular　biomarker-responsive　drug　activation.　This　system　was　composed　of　a　long-nicked　DNA　duplex　formed　by　tandem　hybridization　of　two　extended　antisense　oligonucleotides　whose　ends　were　separately　blocked　with　a　cancer　cell-specific　aptamer,　AS1411,　and　a　replaceable　anti-biomarker　probe　(ABP).　We　demonstrated　that　this　DNA　nanodrug　was　directed　to　cancer　cells　with　the　guidance　power　of　AS1411　and　then　activated　by　the　presence　of　a　given　intracellular　biomarker.　By　using　such　a　belt-and-braces　strategy,　this　DNA　nanodrug　system　could　safely　and　efficiently　accelerate　apoptosis　of　target　cancer　cells.　Moreover,　since　the　expression　level　of　biomarkers　tends　to　indicate　the　specific　physiological　state　of　individual　cells,　biomarker-responsive　activation　of　the　nanodrug　is　expected　to　enable　customized　drug　administration　at　the　cellular　level.