A Novel Biological Nano Confinement Inhibits Cancer Metastasis

Cancer is a complex genetic disease hallmarked with a strong competitive capacity in energy and utilization of substances compared to normal cells, which is partially due to the ability to adjust their metabolism in response to environmental changes. During the lifespan of cancer cells, either during carcinogenesis, progress, or metastasis, massive energy and other substances are essential prerequisites, however, the underlying mechanisms are controversial and still remain unclear. Understanding how cancer cells seize much of the energy and other substances than normal cells is of utmost importance for next-generation cancer therapy, along with the finding of novel drug target and drug design. Recent reports about ‘mitochondrial hijack’ of cancer cells through selfassembled protein nanotubes connected with normal cells and ‘graded messengers pool’ in cytoplasm have evoked a great interest. Considering the widely discussed ‘nanodomain’ in physical and chemical areas, we proposed the concept of biological nano confinement (BNC), by which we may rationally elucidate the priorities of solid tumors on utilization of energy and substances at hypoxia, and less nutrition supplying environments both extraand intra-cellular. The ultimate objective was to address the confusion that CAR-T therapies are effective for hematological cancers but less effective for solid tumors and also to reveal the fact that chimeric antigens receptor-T (CAR-T) adjuvant therapy with chemotherapy has synergetic enhancement effects. In turn, developing novel inhibitors to depolymerize biological nanoconfinement is urgently needed.