Nanomaterial-mediated lactate metabolism regulation for enhanced cancer immunotherapy

Metabolic reprogramming makes tumor cells prefer aerobic glycolysis as the main energy source, resulting in abnormal accumulation of lactate in the tumor microenvironment (TME). Lactate plays a crucial role in regulating cellular metabolism, tumor metastasis and invasion, and immune cell function, and has become an important obstacle in cancer treatment. Therefore, the regulation of lactate in the TME has become a promising target for cancer treatment. Nanomaterials provides a powerful tool for precisely regulating lactate metabolism. Through targeted delivery, controlled release, and multifunctional integration, nanoplatforms can effectively deplete lactate or inhibit its production, thereby reversing the acidic and immunosuppressive state of the TME, and transforming "cold" tumors into immunologically sensitive "hot" tumors. Furthermore, nanomaterials can synergistically interact with metabolic regulation through the catalytic and photothermal properties, inducing immunogenic cell death and activating antitumor immune responses. In view of this, this review summarizes the strategies for regulating lactate mediated by nanomaterials and their effects on antitumor immunity, and discusses their combined potential with immunotherapy. It also analyzes the challenges and future prospects for translating nanomaterials targeting lactate into clinical applications. Nanomaterials are emerging as a bridge connecting tumor metabolic reprogramming and immunotherapy, paving the way for a new paradigm in cancer treatment.