Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer, notable for its strong tendency to metastasize to multiple organs, which contributes to its disproportionately high mortality rate. The complex interactions between TNBC cells and various stromal cells, such as vascular endothelial cells, fibroblasts, and immune cells, collaboratively promote tumor invasiveness, metastatic potential, and drug resistance. The overexpressed intercellular adhesion molecule-1 (ICAM-1, CD54) facilitates the adhesion of tumor cells to vascular endothelial cells and transendothelial migration. Inspired by the physical barrier mechanism of the basement membrane, we propose constructing an in situ biomimetic basement membrane based on the interaction of a fibrillar transformable monopeptide (IFP) and ICAM-1 within tumor tissue to effectively inhibit tumor cell intravasation and angiogenesis. IFP self-assembles into micelles (IFP-NPs) under aqueous conditions, but upon binding to ICAM-1 protein within tumor tissue, transforms into a dense fibrillar network structure, which disrupts homotypic and heterotypic interaction of ICAM-1 between tumor cells and vascular endothelial cells. In vitro and in vivo data confirm that IFP-NPs simultaneously interfere with three key processes of tumor metastasis: angiogenesis, collective invasion, and vascular invasion. The morphological transformation of monopeptides aims to develop a cell engineering approach that achieves sustained modulation of the tumor microenvironment, rather than merely targeting individual signaling pathways, thus potentially avoiding treatment inefficacy caused by signal redundancy.‍‍

全文链接：https://doi.org/10.1016/j.cej.2025.170982