The satisfactory
therapeutic effects of chemodynamic
therapy (CDT) dependent solely on endogenous
hydrogen peroxide (H2O2) from
tumor cells are difficult to achieve. This is closely attributed to the high metabolic activity of malignant
cancer cells, prompting the rapid self-protection and proliferation. Here, we report a programmed self-assembly multilayered nanostructure,
thioglycolic acid (TGA)-Cu coordination nanoparticles with rapid GSH-response characteristics, for intensifying the CDT efficiency and comprehensively inhibiting the
tumor metabolic activity via exchanging the TGA
ligand with
glutathione (GSH) in the
tumor cell. In the formulation, TGA, a small toxic molecule, was combined with Cu
ions and securely delivered to the destination for inactivating the functional
protein by depriving their spatial structure, then inducing the inhibition of metabolism and meiosis. Simultaneously, the oxidative stress that originated from the
oxidized glutathione (
GSSG)-Cu complex triggering H2O2 compels the
cancer cells to perform active and passive death processes in concert with the inhibition of intracellular
enzyme activities. Thus, this work is not only expected to be a heuristic strategy for amplifying the
therapeutic effect of CDT together with the inhibition of
enzyme activity, but also may advance the construction of stimulus-response bio-functional materials.