Lactic Acid

Lactic acid, once considered a mere metabolic waste product, is now recognized as a critical signaling molecule in the tumor microenvironment of hepatocellular carcinoma (HCC). Produced in excess through aerobic glycolysis (the Warburg effect), lactic acid creates an acidic extracellular microenvironment that promotes tumor cell proliferation, angiogenesis, and immune evasion. Lactic acid exerts its effects through three primary pathways: inhibition of the PHD2/VHL system to stabilize HIF-1α, direct binding and activation of the G protein-coupled receptor GPR81, and induction of the newly discovered post-translational modification histone lysine lactylation (Kla). The synergistic action of lactate dehydrogenase (LDH) for production and monocarboxylate transporters (MCTs) for cellular import/export drives the formation of this immunosuppressive niche. Lactic acid potently suppresses immune cell function, including cytotoxic T lymphocytes and natural killer cells, while promoting the recruitment of regulatory T cells and tumor-associated macrophages.

Fig. 1 Lactic Acid in the tumor microenvironment of hepatocellular carcinoma. (Peng X.; et al. 2024)

Lactic acid is the most abundant organic acid in the healthy human vagina, maintaining an acidic pH protective against pathogens. However, lactic acid is incompatible with addition-cure silicone elastomers used for vaginal rings because its carboxylic acid group inhibits the curing reaction. To overcome this limitation, researchers developed a prodrug strategy using DL-lactide, a cyclic lactone dimer of two lactic acid molecules. DL-lactide was successfully incorporated into medical-grade silicone elastomer vaginal rings. Upon release into aqueous medium, lactide rapidly hydrolyzes to produce only lactic acid. The released lactic acid inhibited sperm motility, suppressed HIV-1 and HSV-2 replication, and was active against Gardnerella vaginalis (a causative agent of bacterial vaginosis) while sparing protective lactobacillus species. This prodrug approach enables sustained, controlled release of lactic acid for next-generation multipurpose vaginal rings.

Fig. 2 DL-lactide in medical-grade silicone elastomer vaginal rings. (Bashi Y H D.; et al. 2025)