Nano-Tumor interplay is the basic for most cancers nanotherapy, and the cross-talking of nanomedicines with extracellular matrix (ECM) is more and more thought-about important. Right here, we specifically examine the Nano-ECM interactivity utilizing drug-free nanoparticulates (NPs) and high-metastatic most cancers cells because the fashions. We uncover with shock that NPs carefully bind to particular kinds of ECM elements, retraction fibers (RFs) and migrasomes, which find on the rear of tumor cells throughout their migration. Such interplay is noticed to change cell morphology, restrict cell movement vary and alter cell adhesion. Importantly, NPs are demonstrated in vitro to inhibit tumor cell removing, and their anti-metastasis potentiality is primarily confirmed in vivo. Mechanically, the NPs are discovered to coat and type a inflexible shell on the floor of migrasomes and retraction fibers, by way of the interplay with lipid raft/caveolae substructures. With this, NPs block the popularity, endocytosis and elimination of migrasomes by their surrounding tumor cells. Thereby NPs intervene the cell-ECM interplay and cut back the promotion impact of migrasomes on cell motion. Apart from, NPs set off the expression alteration of proteins associated to cell-cell adhesion and cytoskeleton group, which additionally restricts the cell migration. In abstract, all findings right here present a possible goal for the nanomedicines of anti-tumor metastasis.