Dual inhibition of glycolysis and oxidative phosphorylation by aptamer-based artificial enzyme for synergistic cancer therapy

Dual inhibition of glycolysis and oxidative phosphorylation (OXPHOS) can break the metabolic plasticity of cancer cells to inhibit most energy supply and lead to effective cancer therapy. However, the pharmacokinetic difference among drugs hinders these two inhibitions to realize a uniform temporal and spatial distribution. Herein, we report an aptamer-based artificial enzyme for simultaneous dual inhibition of glycolysis and OXPHOS, which is constructed by arginine aptamer modified carbon-dots-doped graphitic carbon nitride (AptCCN). AptCCN can circularly capture intracellular arginine attribute to the specific binding ability of arginine aptamers to arginine, and further catalyze the oxidation of enriched arginine to nitric oxide (NO) under red light irradiation. In vitro and in vivo experiments showed that arginine depletion and NO stress could inhibit glycolysis and OXPHOS, leading to energy blockage and apoptosis of cancer cells. The presented aptamer-based artificial enzyme strategy provides a new path for cell pathway regulation and synergistic cancer therapy.

Automated summary

In this study, an aptamer-based artificial enzyme was developed to simultaneously inhibit glycolysis and oxidative phosphorylation (OXPHOS) in cancer cells. The artificial enzyme, called AptCCN, can capture intracellular arginine and catalyze its oxidation to nitric oxide (NO) under red light irradiation. In vitro and in vivo experiments demonstrated that this strategy effectively blocked energy supply and induced apoptosis in cancer cells.