Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype characterized by a poor prognosis and resistance to conventional therapies. Peptidylarginine deiminase 4 (PAD4), which catalyzes the conversion of arginine to citrulline, facilitating neutrophil extracellular trap (NET) formation and promoting tumor immune evasion, has been identified as a promising target for TNBC treatment. However, current PAD4 inhibitors have low bioavailability and inadequate stability. Metal-based drugs, particularly ruthenium complexes, exhibit antitumor potential but require injection, limiting their clinical application. Herein, we synthesized a novel metal-based PAD4 inhibitor, BMClRu, for use as an oral TNBC antitumor agent. BMClRu inhibits PAD4, and incorporating ruthenium ligands increases the stability and metabolic resistance of the drug, facilitating oral administration. Furthermore, transmission electron microscopy, immunofluorescence staining, and flow cytometry were used to comprehensively evaluate the nano self-assembly properties, molecular stability, and antitumor efficacy of BMClRu. BMClRu modulates the tumor immune microenvironment by suppressing PAD4-dependent NET formation and inducing immunogenic cell death (ICD), thereby activating antitumor immunity. This study introduces a novel strategy for developing orally bioavailable metal-based antitumor agents as a promising approach for TNBC treatment.Copyright © 2025. Published by Elsevier B.V.