Iron is an essential element for cell proliferation and homeostasis by engaging in cell metabolism including DNA synthesis, cell cycle, and redox cycling; however, iron overload could contribute to tumor initiation, proliferation, metastasis, and angiogenesis. Therefore, manipulating iron metabolisms, such as using iron chelators, transferrin receptor 1 (TFR1) Abs, and cytotoxic ligands conjugated to transferrin, has become a considerable strategy for cancer therapy. However, there remain major limitations for potential translation to the clinic based on the regulation of iron metabolism in cancer treatment. Nanotechnology has made great advances for cancer treatment by improving the therapeutic potential and lowering the side-effects of the proved drugs and those under various stages of development. Early studies that combined nanotechnology with therapeutic means for the regulation of iron metabolism have shown certain promise for developing specific treatment options based on the intervention of cancer iron acquisition, transportation, and utilization. In this review, we summarize the current understanding of iron metabolism involved in cancer and review the recent advances in iron-regulatory nanotherapeutics for improved cancer therapy. We also envision the future development of nanotherapeutics for improved treatment for certain types of cancers.
Keywords: cancer therapy; ferroptosis; iron metabolism; iron reductive therapy; nanodrug delivery system.
© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.