Triple-negative　breast　cancer　(TNBC)　is　highly　aggressive　and　causes　a　higher　proportion　of　metastatic　cases.　However,　therapies　directed　to　specific　molecular　targets　have　rarely　achieved　clinically　meaningful　improvements　in　the　outcome　of　TNBC　therapy.　A　urokinase-type　plasminogen　activator　(uPA),　one　of　the　best-validated　biomarkers　of　breast　cancer,　is　an　extracellular　proteolytic　serine　protease　involved　in　many　pathological　and　physiological　processes,　including　tumor　cell　invasion　and　metastasis.　Nafamostat　mesylate　(NM)　is　a　synthetic　compound　that　inhibits　various　serine　proteases　and　has　been　used　as　a　therapeutic　agent　for　the　treatment　of　TNBC.　Nevertheless,　NM　has　poor　specificity　for　serine　proteases　and　is　easy　be　hydrolyzed;　moreover,　the　inhibitory　mechanism　of　TNBC　therapy　is　unclear.　In　this　study,　we　combine　NM　with　a　macromolecular　drug　delivery　vehicle,　mouse　amino-terminal　fragment　of　urokinase-human　serum　albumin　(mATF-HSA),　to　form　a　complex　(mATF-HSA:NM)　using　the　dilution-incubation-purification　method.　mATF　specifically　targets　uPAR　overexpressed　on　the　surface　of　TNBC　cells;　moreover,　HSA　prevents　NM　from　being　hydrolyzed　by　numerous　serine　proteases.　mATF-HSA:NM　showed　stronger　inhibitory　effects　on　the　proliferation　and　metastasis　of　TNBC　in　vitro　and　in　vivo　without　significant　cytotoxicity　on　normal　cells　and　tissues.　In　addition,　we　demonstrated　that　NM　mediates　metastasis　of　TNBC　cells　through　inhibition　of　uPA　using　a　stable　uPA　knockdown　cell　line　(MDA-MB231　shuPA).　Overall,　we　have　developed　a　macromolecular　complex　targeted　to　treat　high　uPAR-expressing　tumor　types,　and　mATF-HSA　can　potentially　be　used　to　load　other　types　of　drugs　with　tumor-targeting　specificity　for　mouse　tumor　models　and　is　a　promising　tool　to　study　tumor　biology　in　mouse　tumor　models.