Urokinase　plasminogen　activator　receptor　(uPAR)　is　a　key　participant　in　extracellular　proteolysis,　tissue　remodeling　and　cell　motility.　uPAR　overexpresses　in　most　solid　tumors　and　several　hematologic　malignancies,　but　has　low　levels　on　normal　tissues,　thus　is　advocated　as　a　molecular　target　for　cancer　therapy.　One　of　the　obstacles　for　the　evaluation　of　uPAR　targeting　agents　in　preclinical　study　is　the　species　specificity,　where　targeting　agents　for　human　uPAR　usually　not　bind　to　murine　uPAR.　Here,　we　develop　a　targeting　agent　that　binds　to　both　murine　and　human　uPAR.　This　targeting　agent　is　genetically　fused　to　human　serum　albumin,　a　commonly　used　drug　carrier,　and　the　final　construct　is　named　as　uPAR　targeting　carrier　(uPARTC).　uPARTC　binds　specifically　to　uPAR-overexpressing　293T/huPAR　and　293T/muPAR　as　demonstrated　by　flow　cytometry.　A　cytotoxic　compound,　celastrol,　is　embedded　into　uPARTC　non-covalently.　The　resulting　macromolecular　complex　show　effective　proliferation　inhibition　on　both　murine　and　human　uPAR　overexpressing　cells,　and　exhibit　potent　antitumor　efficacy　on　hepatoma　H22-bearing　mice.　This　work　demonstrates　that　uPARTC　is　a　promising　tumor　targeting　drug　carrier,　which　address　the　species-specificity　challenge　of　uPAR　targeting　agents　and　can　be　used　to　load　other　cytotoxic　compounds.　©　2023