Chemotherapy　is　commonly　used　to　treat　malignant　tumors.　However,　conventional　chemotherapeutic　drugs　often　cannot　distinguish　between　tumor　and　healthy　cells,　resulting　in　adverse　effects　and　reduced　therapeutic　efficacy.　Therefore,　zigzag-shaped　gear-occlude-guided　cymbal-closing　(ZGC)　DNA　nanotechnology　was　developed　based　on　the　mirror-symmetry　principle　to　efficiently　construct　symmetric　DNA　polyhedra.　This　nanotechnology　employed　simple　mixing　steps　for　efficient　sequence　design　and　assembly.　A　targeting　aptamer　was　installed　at　a　user-defined　position　using　an　octahedron　as　a　model　structure.　Chemotherapeutic　drug-loaded　polyhedral　objects　were　subsequently　delivered　into　tumor　cells.　Furthermore,　anticancer　drug-loaded　DNA　octahedra　were　intravenously　injected　into　a　HeLa　tumor-bearing　mouse　model.　Assembly　efficiency　was　almost　100　%,　with　no　residual　building　blocks　identified.　Moreover,　this　nanotechnology　required　a　few　DNA　oligonucleotides,　even　for　complex　polyhedrons.　Symmetric　DNA　polyhedrons　retained　their　structural　integrity　for　24　h　in　complex　biological　environments,　guaranteeing　prolonged　circulation　without　drug　leakage　in　the　bloodstream　and　promoting　efficient　accumulation　in　tumor　tissues.　In　addition,　DNA　octahedra　were　cleared　relatively　slowly　from　tumor　tissues.　Similarly,　tumor　growth　was　significantly　inhibited　in　vivo,　and　a　therapeutic　outcome　comparable　to　that　of　conventional　gene-chemo　combination　therapy　was　observed.　Moreover,　no　systemic　toxicity　was　detected.　These　findings　indicate　the　potential　application　of　ZGC　DNA　nanotechnology　in　precision　medicine.　©　2024　Elsevier　Inc.