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.

The promising potential of photodynamic therapy (PDT) has fueled the development of minimally invasive therapeutic approaches for cancer therapy. However, overcoming limitations in PDT efficacy in the hypoxic tumor environment and light penetration depth remains a challenge. We report the engineering of tungsten carbide nanoparticles (W₂C NPs) for 1, 064 nm laser-activated dual-type PDT and combined theranostics. The synthesized W₂C NPs allow the robust generation of dual-type reactive oxygen species, including hydroxyl radicals (type Ⅰ) and singlet oxygen (type Ⅱ), using only single 1, 064 nm laser activation, enabling effective PDT even in the hypoxic tumor environment. The W₂C NPs also possess high photothermal performance under 1, 064 nm laser irradiation, thus enabling synergistically enhanced cancer therapeutic efficacy of PDT and photothermal therapy. Additionally, the photoacoustic and X-ray computed tomography bioimaging properties of W₂C NPs facilitate the integration of tumor diagnosis and therapy. The developed W₂C based theranostic nanoagents increase the generation of reactive oxygen species in hypoxic tumors, improve the light penetration depth, and facilitate combined photothermal therapy and photoacoustic/computed tomography dual-mode bioimaging. These attributes could spur the exploration of transition metal carbides for advanced biomedical applications.