A　novel　cyclodextrin-containing　star　polymer　was　synthesized　by　atom　transfer　radical　polymerization　using　the　arm-first　approach.　Copolymerization　of　a　mixture　of　mono-　and　multi-methacrylate　substituted　cyclodextrin　and　2-(dimethylamino)　ethyl　methacrylate　initiated　by　poly(ethylene　glycol)　macroinitiator　produced　a　core　cross-linked　star　polymer.　The　star　polymer　could　self-assemble　into　nanostructures　via　host-guest　interactions　between　the　cyclodextrin　polymer　and　hydrophobic　guest　molecules.　The　morphologies　of　these　nanostructures　showed　regular　transitions　by　altering　the　type　of　guest　molecule,　the　ratio　of　star　polymer　to　guest,　and　the　pH　of　the　solution.　Furthermore,　doxorubicin　(DOX)　was　entrapped　into　the　star　polymer　for　the　purpose　of　drug　delivery.　In　vitro　experiments　demonstrated　that　the　DOX-loaded　nanoparticles　could　release　their　payload　in　response　to　the　endosomal-pH　after　being　internalized　by　HeLa　cell　via　endocytosis.　At　high　DOX　concentration,　DOX-loaded　nanoparticles　showed　significantly　higher　cell　cytotoxicity　compared　to　the　free　drug.　The　results　indicate　that　the　star　polymer　has　great　promise　for　potential　anticancer　treatment.　©　2013　The　Royal　Society　of　Chemistry.