We covalently tethered the POI ligand to heat shock protein 90 (HSP90) within platelets through ligand-directed covalent labeling method mediated by the N-acyl-N-alkyl sulfonamide (NASA) linker. These proteolytic platelets, termed DePLT, could selectively accumulate at wound-associated disease sites and then potently degrade the POI by repurposing the critical role of molecular chaperones in protein processing.