The　structural　DNA　nanotechnology　holds　great　potential　application　in　bioimaging,　drug　delivery　and　cancer　therapy.　Herein,　an　intelligent　aptamer-incorporated　DNA　nanonetwork　(Apt-Nnes)　is　demonstrated　for　cancer　cell　imaging　and　targeted　drug　delivery,　which　essentially　is　a　micron-scale　pattern　with　the　thickness　of　double-stranded　monolayer.　Cancer　cell-surface　receptors　can　make　it　perform　magical　transformation　into　small　size　of　nanosheet　intermediates　and　specifically　enter　target　cells.　The　binding　affinity　of　Apt-Nnes　is　increased　by　3-fold　due　to　multivalent　binding　effect　of　aptamers　and　it　can　maintain　the　structural　integrity　in　fetal　bovine　serum　(FBS)　for　8　h.　More　interestingly,　target　cancer　cells　can　cause　the　structural　disassembly,　and　each　resulting　unit　transports　4963　doxorubicin　(Dox)　into　target　cells,　causing　the　specific　cellular　cytotoxicity.　The　cell　surface　receptor-mediated　disassembly　of　large　size　of　DNA　nanostructures　into　small　size　of　fractions　provides　a　valuable　insight　into　developing　intelligent　DNA　nanostructure　suitable　for　biomedical　applications.　©　2022　Elsevier　Inc.