This article presents a novel approach to tumor therapy using a sequential catalytic nanomedicine system. The researchers developed a biocompatible nanocatalyst composed of natural glucose oxidase (GOD) and ultrasmall Fe₃O₄ nanoparticles (Fe₃O₄ NPs) integrated into large-pore dendritic silica nanoparticles (DMSNs). The system works by first depleting glucose in tumor cells through GOD, generating hydrogen peroxide (H₂O₂), which is then catalyzed by Fe₃O₄ NPs to produce highly toxic hydroxyl radicals (·OH) under the mildly acidic tumor microenvironment. These radicals induce apoptosis and death of tumor cells, offering a targeted and efficient therapeutic strategy. The nanocatalyst is designed to exploit the unique metabolic characteristics of tumor cells, which have a higher glucose consumption rate and produce a mildly acidic environment. This enables the sequential catalytic reactions to occur specifically in the tumor microenvironment, minimizing damage to normal tissues. The system demonstrates high biocompatibility and efficient tumor suppression in both in vitro and in vivo studies. In vitro experiments show that the nanocatalyst effectively generates hydroxyl radicals, leading to significant cell death in cancer cells. In vivo studies on 4T1 mammary tumor and U87 glioblastoma xenograft models demonstrate that the nanocatalyst significantly reduces tumor size and weight, with minimal toxicity to normal tissues. The biodegradation behavior of the nanocatalyst is also favorable, with minimal damage to major organs and high biocompatibility. The study highlights the potential of sequential catalytic nanomedicine as a promising strategy for efficient and targeted tumor therapy, combining the advantages of catalytic reactions with the specificity of the tumor microenvironment. The results suggest that this approach could offer a safer and more effective alternative to traditional cancer therapies.This article presents a novel approach to tumor therapy using a sequential catalytic nanomedicine system. The researchers developed a biocompatible nanocatalyst composed of natural glucose oxidase (GOD) and ultrasmall Fe₃O₄ nanoparticles (Fe₃O₄ NPs) integrated into large-pore dendritic silica nanoparticles (DMSNs). The system works by first depleting glucose in tumor cells through GOD, generating hydrogen peroxide (H₂O₂), which is then catalyzed by Fe₃O₄ NPs to produce highly toxic hydroxyl radicals (·OH) under the mildly acidic tumor microenvironment. These radicals induce apoptosis and death of tumor cells, offering a targeted and efficient therapeutic strategy. The nanocatalyst is designed to exploit the unique metabolic characteristics of tumor cells, which have a higher glucose consumption rate and produce a mildly acidic environment. This enables the sequential catalytic reactions to occur specifically in the tumor microenvironment, minimizing damage to normal tissues. The system demonstrates high biocompatibility and efficient tumor suppression in both in vitro and in vivo studies. In vitro experiments show that the nanocatalyst effectively generates hydroxyl radicals, leading to significant cell death in cancer cells. In vivo studies on 4T1 mammary tumor and U87 glioblastoma xenograft models demonstrate that the nanocatalyst significantly reduces tumor size and weight, with minimal toxicity to normal tissues. The biodegradation behavior of the nanocatalyst is also favorable, with minimal damage to major organs and high biocompatibility. The study highlights the potential of sequential catalytic nanomedicine as a promising strategy for efficient and targeted tumor therapy, combining the advantages of catalytic reactions with the specificity of the tumor microenvironment. The results suggest that this approach could offer a safer and more effective alternative to traditional cancer therapies.