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Metabolic reprogramming allows tumor cells to prefer aerobic glycolysis as the main energy source, resulting in the massive accumulation of lactate in the tumor microenvironment (TME). It is found that lactate is no longer a waste product produced by glycolysis, but plays an important role in cancer progression. The modulation of lactate in the TME has become a promising target for cancer therapy. Although many small molecular inhibitors modulating the production or transport of lactate have appeared at present, their safety and efficacy have limited their further clinical application due to their non-specific targets and biodistribution. Studies have shown that nanomedicine has unique advantages, improving drug delivery efficiency and treatment efficacy while reducing damage to normal tissues, which greatly promotes the development of the research of nanosystems based on lactate modulation. In this review, we summarize the source and metabolism of lactate, the effect of lactate on the TME and recent advances in nanosystem-mediated strategies of lactate modulation for enhanced cancer therapy, hoping to provide ideas and directions for future research in related fields.
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