Cascade-enzyme reaction systems have emerged as promising
tools
for treating malignant tumors by efficiently converting nutrients
into toxic substances. However, the challenges of poor localized retention
capacity and utilization of highly active enzymes often result in
extratumoral toxicity and reduced therapeutic efficacy. In this study,
we introduced a cell membrane–DNA nanoanchor (DNANA) with a
spatially confined cascade enzyme for in vivo tumor therapy. The DNANAs
are constructed using a polyvalent cholesterol-labeled DNA triangular
prism, ensuring high stability in cell membrane attachment. Glucose
oxidase (GOx) and horseradish peroxidase (HRP), both modified with
streptavidin, are precisely confined to biotin-labeled DNANAs. Upon
intratumoral injection, DNANA enzymes efficiently colonize the tumor
site through cellular membrane engineering strategies, significantly
reducing off-target enzyme leakage and the associated risks of extratumoral
toxicity. Furthermore, DNANA enzymes demonstrated effective cancer
therapy in vitro and in vivo by depleting glucose and producing highly
cytotoxic hydroxyl radicals in the vicinity of tumor cells. This membrane-engineered
cascade-enzyme reaction system presents a conceptual approach to tumor
treatment.