Cascade Enzymes Confined in DNA Nanoanchors for Antitumor Therapy.
Danyu WangXin ZhouMengyu HuangJie DuanYue QiuHua YiYang WangHuimin XueJiali ZhangQiuxia YangHua GaoZhenzhen GuoKaixiang ZhangPublished in: ACS applied materials & interfaces (2024)
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.
Keyphrases
- circulating tumor
- cell free
- cancer therapy
- single molecule
- oxidative stress
- drug delivery
- blood glucose
- pet imaging
- metabolic syndrome
- heavy metals
- wastewater treatment
- nucleic acid
- type diabetes
- hydrogen peroxide
- nitric oxide
- risk assessment
- skeletal muscle
- climate change
- smoking cessation
- circulating tumor cells
- combination therapy