Influence of cell force-driven piezoionic hydrogels on the migration of cancer cells

Cancer metastasis presents a formidable clinical challenge, demanding innovative therapeutic approaches. Compared to normal cells, the enhanced migratory capacity of malignant cancer cells plays a pivotal role in the metastatic process. Targeting this differential motility to inhibit migration may offer a novel strategy for cancer treatment. We found that the piezoionic hydrogels significantly inhibited the migration of human hepatocellular carcinoma cells (Huh-7) which are characterized by high migratory capacity, with minimal impact on normal cell migration. Cell adhesion genes like ICAM1 increased and N-cadherin decreased on the piezoionic hydrogel. Besides, piezoionic hydrogels induced calcium overload in cancer cells by activating Piezo1 and promoting excessive calcium influx, which can disrupt mitochondrial function and compromise cytoskeletal integrity, ultimately hindering cell migration. Crucially, our research has pioneered the validation of a novel strategy: harnessing the inherent migratory properties of cancer cells to suppress their own migration, while exerting minimal inhibitory effects on normal cells with weaker migratory capabilities, may offer a superior method and strategy for specifically targeting and inhibiting malignant cancer cell metastasis.