Coagulation-Targeted TGF-β Signaling Pathway Inhibitor Nanomedicine for Inhibiting the Growth and Lung Metastasis of Breast Cancer
Yajun Xu, Jianlin Lv, Ya Liu, Jincheng Du, Chuwen Luo, Ying Wang, Linlin Liu, Kazuo Sakurai, Zhaohui Tang, Xuesi Chen
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 mm 3, 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.