Wang Danyu, Zhou Xin, Huang Mengyu, Duan Jie, Qiu Yue, Yi Hua, Wang Yang, Xue Huimin, Zhang Jiali, Yang Qiuxia, Gao Hua, Guo Zhenzhen, Zhang Kaixiang
Henan Key Laboratory of Nanomedicine for Targeting Diagnosis and Treatment, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
Institute of Biomedical Engineering, College of Life Sciences, Qingdao University, Qingdao 266071, China.
ACS Appl Mater Interfaces. 2024 Sep 25;16(38):50295-50304. doi: 10.1021/acsami.4c09835. Epub 2024 Sep 12.
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.
