Nanomedicine-based lactate metabolism and lactylation regulation for exploring new therapeutic strategies in cancer.

Lactate, a key metabolite of glycolysis in tumor cells, plays a dual role in cancer progression. On one hand, it contributes to the formation of an acidic tumor microenvironment that fosters tumorigenesis and malignancy. On the other, it promotes tumor progression through protein lactylation, a recently identified post-translational modification. Consequently, targeting lactate metabolism and lactylation represents a critical therapeutic method in oncology. Advances in nanomedicine have opened new possibilities for precise modulation of lactate metabolism. Nanomedicine-based strategies enable the regulation of lactate production, transport, and clearance, thereby offering effective tools for tumor suppression. Additionally, the lactate induced lactylation orchestrated by lactyl-CoA, lactyltransferases, and delactylases offer more refined targets for investigating approaches to inhibit tumor progression. In this review, we comprehensively summarize recent developments in nanomedicine-based strategies for lactate metabolism modulation and the mechanism of lactylation regulation. We suppose the design of multifunctional nanoplatforms capable of simultaneously regulating lactate levels and lactylation could integrate metabolic and epigenetic interventions to disrupt lactate-driven tumor support mechanisms precisely and effectively for advancing cancer treatment paradigms.