Framework nucleic acid-based confined enzyme cascade for efficient synergistic cancer therapy in vivo

• 作者: Gezhi Kong Meng Zhang Mengyi Xiong Mei Chen Chan Yang Yan Zhao Yue Yang Zilong Zhao Zhi-Ling Song Liang Gong Guoliang Ke Xiao-Bing Zhang Weihong Tan
• 来源期刊: 中国科学：化学（英文版）
• 年，卷（期）: 2021,（4）
• 所属期刊栏目: ARTICLES
• 页码范围: 660-665
• 页数: 6页
• 语种: 英文

摘要

Artificial enzyme cascade systems with confinement effect are highly important in synthetic biology and biomedicine.Herein,a framework nucleic acid-based confined enzyme cascade (FNA-CEC) for synergistic cancer therapy in vivo was developed.The FNA-CEC consisted of glucose oxidase and horseradish peroxidase precisely assembled on an addressable DNA tetrahedron scaffold within few nanometers.Glucose oxidase (GOx) can trigger efficient glucose depletion for tumor starvation therapy,and increase the local concentration of H2O2 in situ for enhanced downstream horseradish peroxidase (HRP)-activated prodrug therapy.Due to the spatial-confinement on DNA tetrahedron scaffold,the efficiency of intermediate metabolites transportation between the enzyme cascades was improved.Moreover,FNA-CEC was applied for efficient synergistic cancer therapy in vitro and in vivo.As a simple and efficient approach,the FNA-CEC is expected to expand the toolbox of technologies in synthetic biology and biomedicine.