Triple　negative　breast　cancer　(TNBC)　is　one　kind　of　breast　cancer　that　demonstrates　highly　aggressive　tumor　biology.　The　high　heterogeneity　of　TNBC　makes　its　individual　clinical　treatment　extremely　blind　and　limited,　which　also　introduces　more　challenges　into　the　diagnosis　and　treatment　of　diseases.　Urokinase-type　plasminogen　activator　(uPA)　is　a　high　level　marker　for　breast　cancer,　which　mediates　tumor　growth　and　metastasis.　Quercetin　is　a　plant-derived　flavonoid　in　many　plants,　which　inhibits　uPA　and　has　low　bioavailability　and　mediocre　pharmaceutical　efficacy.　Thus,　we　herein　developed　polymeric　nanoparticulate　systems　from　PLGA-TPGS　(Qu-NPs)　for　quercetin　oral　delivery　and　evaluated　the　anticancer　effect　of　this　formulation　on　TNBCin　vitroandin　vivo.　Qu-NPs　have　a　uniform　spherical　morphology　with　a　mean　diameter　of　198.4　±　7.8　nm　and　good　drug　loading　capacity　(8.1　±　0.4%).　Moreover,　Qu-NPs　exhibited　significantly　improved　inhibition　on　the　growth　and　metastasis　in　TNBC　cells.　Following　oral　gavage,　a　remarkable　antitumor　effect　of　Qu-NPs　on　4T1-bearing　mice　was　observed　with　a　tumor　inhibition　ratio　of　67.88%　and　fewer　lung　metastatic　colonies.　Furthermore,　the　inhibitory　effect　of　quercetin　on　the　migration　of　uPA　knockdown　MDA-MB231　cells　was　greatly　attenuated.　Together,　Qu-NPs　improved　the　significant　antitumor　and　antimetastatic　effects　by　inhibiting　uPA,　which　provides　a　new　strategy　for　the　treatment　of　TNBC.　©　The　Royal　Society　of　Chemistry　2020.