Regulating metalloimmunology with nanomedicine for cancer therapy

Metals are essential components of both micronutrients and macronutrients in living organisms and are involved in a variety of immune processes in the forms of free ions or protein-coupled complexes (metalloproteins). Multiple aspects of the immune system, from the structural and functional control of immune-related proteins to the cellular responses to immunotherapy, could be affected by metals. Therefore, the employment of metal for the regulation of immunity, termed as metalloimmunology, is gaining interest as a prevalent and efficacious approach to combating cancer. However, the manipulation of metalloimmunology using traditional drugs presents several challenges, including limited bioavailability, adverse effects, and a lack of targeting specificity. This review provides an overview of the latest findings in metal and metal-regulatory therapeutic agents for the treatment of cancer. Essential trace metal elements, such as iron, zinc, copper, manganese, magnesium, and calcium, as well as heavy metal drugs and their mechanisms of action, will be discussed with a particular focus on their roles in regulating the tumor-immune interplay. The latest nanotechnology employed in the administration of metal-regulatory drugs and the design concepts for tailored therapeutic interventions will be discussed. These concepts and information offer promising clinical possibilities of modulating cancer immunology by targeting metal metabolism.