Luteolin- and silibinin-co-loaded with SDPN alleviated breast cancer metastasis in 4T1 tumor-bearing mice by regulating the conversion of tumor-associated M2 macrophages into the M1 phenotype and reducing the proportion of the M2-phenotype through co-action on STAT3 and HIF-1α. Here, HIF1A is linked to breast carcinoma.