Synergistic disruption of redox and energy homeostasis via high-entropy layered double hydroxide nanozymes for enhanced tumor therapy

Abstract

Summary The efficacy of nanozyme catalytic therapy is often affected by the complexity of tumor microenvironment (TME), since tumors use energy metabolism to resist oxidative stress. Relying only on disrupting the redox balance is usually not enough to completely remove the tumor. To address this problem, a high-entropy engineering strategy was developed to build a Pt-LDH nanozyme, where Pt clusters are anchored onto a high-entropy layered double hydroxide (LDH) support. This design endows the Pt-LDH with glucose oxidase (GOx)-like activity, which directly consumes intratumoral glucose to cut off the energy supply, overcoming the limitation of insufficient endogenous oxidants and stimulated subsequent oxidative stress. By simultaneously disrupting the energy metabolism and homeostasis, the Pt-LDH nanozyme achieves a potent synergistic therapeutic effect. Both in vitro and in vivo studies showed that Pt-LDH inhibited tumor growth with minimal toxicity. This proves that high-entropy design can be a powerful and practical way to build nanozyme for cancer therapy.