A　novel　long-circulating　and　pH-responsive　dendrimer　nanocarrier　was　prepared　for　delivering　5-fluorouracil　(5-FU)　to　tumors　through　the　targeting　of　nanoparticles　to　the　low　pH　environment　of　tumors.　The　nanocarrier,　poly(2-(N,N-diethylamino)ethyl　methacrylate)　with　methoxy-poly(ethylene　glycol)poly(amidoamine)(PPD),　had　a　core-shell　structure　with　4.0　G　poly(amidoamine)　(PAMAM)　as　the　core　and　parallel　poly(2-(N,N-diethylamino)ethyl　methacrylate)　(PDEA)　chains　and　methoxy-poly(ethylene　glycol)　(mPEG)　chains　as　the　shell.　The　PDEA　chain　was　pH-responsive,　and　the　PEG　chains　led　to　long　circulation　in　blood　vessels　to　achieve　tumor　targeting.　The　sizes,　drug　encapsulation　and　release　of　PPD　nanocarriers　showed　high　pH-dependency　due　to　the　PDEA　chains,　as　they　were　hydrophilic　at　pH　6.5　and　hydrophobic　at　pH　7.4.　The　encapsulation　efficiency　of　5-FU　in　PPD　nanocarriers　was　as　high　as　92.5%　through　the　pH　transition.　The　release　of　5-FU　from　PPD　nanocarriers　was　much　faster　at　pH　6.5　than　at　pH　7.4.　The　5-FU-loaded　nanocarrier　had　a　long　half-life　after　intravenous　administration　in　mice　and　showed　high　tumor　targeting.　This　nanocarrier　composite　also　showed　enhanced　anticancer　effects.　PPD　is　a　promising　nanocarrier　of　anticancer　drugs　with　high　encapsulation,　tumor　targeting　and　pH-responsive　release　in　tumors.　(c)　2011　Elsevier　B.V.　All　rights　reserved.