Novel Insight into Blocking Cancer Metastasis by Biological Nano Confinement through Altering the Cancer Microenvironment

Cancer is a devastating disease marked by a strong competitive capacity in energy and substance utilization in cancer cells compared to that in normal cells. This is partially due to the ability to adjust their metabolism in response to environmental changes. During the lifespan of a cancer cell, massive energy and substance demands are observed either in carcinogenesis, progress, or metastasis; however, the mechanisms involved are controversial and remain unclear. Understanding how cancer cells seize more energy and substances than normal cells is necessary for developing next-generation cancer therapy, including finding novel drug targets and designing drugs. Recent reports about mitochondrial hijack of cancer cells through self-assembled protein nanotubes connected with normal cells and graded messengers pool in the cytoplasm have evoked great interest. Considering the widely discussed nanodomain in physical and chemical areas in this perspective, biological nano confinement (BNC) was rationally discussed. We discuss various aspects such as the tendency of solid cancer cells to prioritize and utilize energy and substances at hypoxia while creating a lesser nutrition-supplying environment extra- and intra-cellularly, the paradox that chimeric antigen receptor T (CAR-T) therapies are effective in hematological cancers but less effective in solid tumors, and the fact that CAR-T adjuvant therapy with chemotherapy has synergetic enhancement effects. In addition, we concluded that developing novel inhibitors to depolymerize biological nanoconfinement is urgently needed.