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Typical features of TME include moderate acidity (pH 6.57.0), excessive secretion of reactive oxygen species (such as H 2 O 2 ), and reducing molecules (such as glutathione and GSH) ( 2.3.1 pH-responsive NDDS Even when oxygen is plentiful, tumor cells tend to metabolize glucose through glycolysis rather than efficient oxidative phosphorylation

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Previous studies have shown that inhibiting SIRT2 may enhance the stability of glucokinase (GCK) regulatory proteins, accelerate aldolase A degradation, and inhibit -cell insulin secretion via modulation of the Akt/glycogen synthase kinase-3 (GSK3)/-catenin pathway, collectively reducing glycolytic flux (42)