Novel　amphiphilic　copolymer　nanoparticles　(HPAE-co-PLA-DPPE)　composed　of　hyperbranched　poly　(amine-ester),　polylactide　and　1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine　(DPPE)　segments　were　designed　and　synthesized　that　provided　high　encapsulation　efficiency.　These　nanoparticles　(NPs)　were　used　to　encapsulate　an　antitumor　model　drug,　doxorubicin　(DOX).　The　resulting　NPs　exhibited　high　encapsulation　efficiency　to　DOX　under　an　appropriate　condition.　In　vitro　release　experiments　revealed　that　the　release　of　DOX　from　NPs　was　faster　at　pH　4.5　than　that　at　pH　7.4　or　pH　6.0.　Confocal　microscopy　observation　indicated　that　the　DOX-loaded　NPs　can　enter　cells　and　localize　in　lysosomes　that　can　be　released　quickly　into　the　cytoplasm.　The　DOX-loaded　NPs　showed　comparable　anticancer　efficacy　with　the　free　drug　both　in　vivo　and　in　vitro.　These　results　demonstrate　a　feasible　application　of　the　hyperbranched　copolymer,　HPAE-co-PLA-DPPE,　as　a　promising　nanocarrier　for　intracellular　delivery　of　antitumor　drugs.　From　the　Clinical　Editor:　In　this　paper,　the　development　of　novel　amphiphilic　copolymer　nanoparticles　is　discussed　with　the　goal　of　establishing　high　encapsulation　efficiency　for　chemotherapy　drugs.　(C)　2011　Elsevier　Inc.　All　rights　reserved.