An energy metabolism blockade and redox homeostasis imbalance dual-pathway strategy for H2S gas-bloomed calcium overload
image: The hollow-hierarchical multistage H2S blasting nanomedicine possesses the capability to respond to both glutathione and tumor microenvironment stimuli, thereby enabling an H2S gas-bloomed calcium overload synergistic therapeutic approach that forms a multimodal synergistic energy metabolism and bidirectional redox homeostasis imbalance storm.
Credit: Harbin Engineering University
Hydrogen sulfide (H2S)-based mitochondrial energy metabolism blockade is an attractive tumor therapeutic modality. However, it is limited owing to metabolic plasticity, which allows tumors to shift their metabolic phenotype between oxidative phosphorylation and glycolysis for energy compensation. To break through this bottleneck, Prof. Piaoping Yang and Prof. He Ding from Harbin Engineering University have designed a hollow-hierarchical multistage H2S blasting nanomedicine DMOS-PB&PAA-Ca&GOx@PEG (DPCG NPs) for tumor therapy by using the dual strategy of energy metabolism blockade and redox homeostasis imbalance to achieve the dual strategy of blocking energy metabolism process, amplifying cascade effect of oxidative stress and finally activating cell death pathway. Prospectively, the dual-pathway strategy targeting energy metabolism blockade and redox homeostasis imbalance will ultimately deplete the energy reserves of tumor cells, providing new insights for the exploration of bioenergetic inhibition as a therapeutic approach.
This work was supported by the National Natural Science Foundation of China (22205048 and U22A20347), the China Postdoctoral Science Foundation (2023T160154), the Heilongjiang Postdoctoral Science Foundation (LBH-TZ2406), the Young Elite Scientists Sponsorship Program of Heilongjiang (2024QNTJ001), and the Fundamental Research Funds for the Central Universities.