This system encapsulates the palmitoylation inhibitor 2-BP within poly(lactic-co-glycolic acid) (PLGA) nanoparticles coated with tumor-derived membranes (MD), simultaneously enhancing afatinib’s (AFT) therapeutic efficacy against TNBC cells while blocking PD-1/PD-L1 checkpoint signaling. Here, CD274 is linked to neoplasm.