Baicalin　(BAI)　has　been　reported　to　exert　antitumor　effects.　However,　BAI　has　limited　water　solubility,　nonspecific　tumor　targeting,　and　low　bioavailability,　which　severely　limited　its　clinical　application.　The　aim　of　this　study　was　to　develop　folic　acid　(FA)　covalently　conjugated-polyamidoamine　(PAMAM)　dendrimers　(PAMAMFA)　as　carrier　systems　for　improvement　of　water　solubility　and　tumor-specificity　of　BAI,　and　study　the　role　of　generation　on　the　physiochemical　properties　and　biological　effects　of　PAMAM-FA/BAI　complexes.　In　this　work,　four　generations　of　PAMAM-FA　were　synthesized　to　entrap　BAI.　The　average　sizes　of　G3-FA/BAI,　G4-FA/BAI,　G5-FA/　BAI,　and　G6-FA/BAIcomplexes　were　174.4　nm,　184.5　nm,　258.8　nm,　and　2475　nm,　respectively,　and　the　zeta　potentials　of　four　PAMAM-FA/BAI　complexes　were　2.9　mV,　6.6　my,　93　mV,　9.0　mV,　respectively.　The　entrapment　efficiencies　of　four　PAMAM-FA/BAI　complexes　were　91.1%,　53.5%,　803%,　and　91.9%,　respectively,　and　the　drug　loading　of　PAMAM-FA/BAI　complexes　were　about　22%.　The　formed　PAMAM-FA/BAI　complexes　allowed　sustained　release　of　BAI　in　acidic　PBS　(pH　5.4).　In　cellular　uptake　assay,　PAMAM-FA/BAI　complexes　demonstrated　increased　drug　uptake　level　in　folate　receptor　(FR)-positive　Hela　cancer　cells　than　FR-negative　A549　cells,　and　the　cellular　uptake　efficiency　of　PAMAM-FA　is　closely　related　with　the　generation　of　PAMAM.　The　Mn　assay　results　showed　that　PAMAM-FA/BAI　complexes　demonstrated　enhanced　toxicity　against　Hela　cells　than　non-FA-modified　PAMAM/BAI　complexes,　and　the　G6-FA/BAI　demonstrated　the　best　inhibition　efficiency.　The　cell　cycle　and　cell　apoptosis　analysis　further　demonstrated　the　tumor-specific　therapeutic　efficacy　of　PAMAM-FA/BAI.　These　results　suggested　that　the　PAMAM-FA　have　the　potential　for　targeted　delivery　of　BAI　into　cancer　cells　to　enhance　its　anti-tumor　efficacy.　(C)　2017　Elsevier　B.V.　All　rights　reserved.