Nanomaterial-Mediated Metabolic Modulation of Immune Responses: Mechanisms and Therapeutic Perspectives

Abstract: Dysregulated immune responses drive the onset and progression of inflammatory, autoimmune, and metabolic diseases. Emerging evidence identifies cellular metabolism as a central regulatory hub of immune responses, where it not only meets the bioenergetic and biosynthetic demands of immune cells but also generates metabolites that shape their fate and function. Nanomaterials have long been explored as modulators of immune responses, yet most studies have focused primarily on cytokines and classical signaling pathways. Consequently, how nanomaterials shape immune responses through metabolic pathways remains relatively underexplored. Emerging evidence has recently identified metabolism as a critical axis through which nanomaterials can modulate immune responses, supporting a shift from conventional immune modulation toward integrated immune–metabolic regulation. Their tunable size, charge, and surface chemistry allow nanomaterials to interact with intracellular organelles such as mitochondria, thus altering the local metabolic flux. In this review, we summarize the current progress in nanomaterial-mediated immunometabolic regulation, focusing on major metabolic pathways including glycolysis, lipid metabolism, the TCA cycle, and OXPHOS, through which nanomaterials modulate immune cell activation, differentiation, and cytokine production. Finally, we highlight how the metabolism-modulating capacity of nanomaterials provides opportunities for the rational design of biomaterials targeting immune metabolism, with therapeutic potential for inflammatory and metabolic diseases. Keywords: metabolic pathways, immunotherapy, immune cells, nanomaterials