Researchers used lipid nanoparticles to deliver nicotinamide mononucleotide (NMN) to natural killer cells in solid tumors, restoring intracellular NAD+ levels that lactate-rich tumor microenvironments deplete. By simultaneously deploying dichloroacetate via engineered exocytic pathways to reduce lactate, the approach rewires cellular metabolism, extends NK cell persistence, and reactivates anti-tumor cytolytic function. This dual-compartment strategy demonstrates how metabolic reprogramming via NAD+ restoration can overcome immunosuppression in adoptive cell therapies, with potential applications across T cell and macrophage therapies.
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NMN-loaded nanoparticles restored NK cell NAD+ and cytolytic function in solid tumour models, supporting NAD+ repletion as a metabolic support strategy.