Coagulation-Targeted TGF-β Signaling Pathway Inhibitor Nanomedicine for Inhibiting the Growth and Lung Metastasis of Breast Cancer.

Abstract

The transforming growth factor β (TGF-β) signaling pathway exerts a dual role in oncogenesis, acting as a suppressor in healthy and early stage neoplastic tissues while promoting malignancy and metastasis in advanced cancers. Tumor hemorrhage further exacerbates TGF-β-mediated metastasis by up-regulating its expression. Here, a coagulation-targeting peptide (A15)-decorated TGF-β inhibitor nanomedicine (A15-LY-NPs) was developed. The tumor colonization assays showed that the nanomedicine reduced 4T1-luc cell colonization in normal tissues. When combined with a vascular disrupting agent, A15-LY-NPs demonstrated three times greater drug accumulation in the tumor at 24 h compared to the control and showed a 93.7% tumor suppression rate in 4T1 tumors initiated at ∼500 mm³, significantly attenuating metastatic spread to the lungs and liver. This study presents an innovative approach for the precise and efficient delivery of TGF-β inhibitors to tumors, offering the potential to augment the efficacy of cancer therapeutics.