Missing-linker-assisted artesunate delivery by metal-organic frameworks for synergistic cancer treatment

• Main Authors: Wang, Dongdong, He, Isabel Wenjia, Liu, Jiawei, Jana, Deblin, Wu, Yinglong, Zhang, Xiaodong, Qian, Cheng, Guo, Yi, Chen, Xiaokai, Bindra, Anivind Kaur, Zhao, Yanli
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2022
• Subjects: Science::Chemistry; Artesunate; Metal–Organic Framework
• Online Access: https://hdl.handle.net/10356/155942
• Institution: Nanyang Technological University

Clinical translation of artesunate (ATS) as a potent antitumor drug has been obstructed by its rapid degradation and low bioavailability. Herein, we report the development of ATS nanomedicine through the self-assembly with Mn[Co(CN)6]2/31/3 metal-organic frameworks (MOFs) having hidden missing linkers. The defects originated from the missing linkers play a key role in increasing the biological stability and tumor accumulation of ATS. Chlorin e6 (Ce6) and ATS can be co-loaded into MOFs for a synergistic antitumor efficacy. In the presence of intracellular HCO3-, Mn2+ acts as an efficient catalyst to promote the bicarbonate-activated H2O2 system and induce oxidative death to cancer cells based on ATS with an endoperoxide bridge. The released [CoIII(CN)6] linker undergoes a redox reaction with intracellular glutathione to prevent the scavenging ability of reactive oxygen species, contributing to synergistic chemodynamic therapy of ATS and photodynamic therapy of Ce6. Thus, defect-engineered MOFs with hidden missing linkers hold great promises in advancing the practical uses of ATS as an antitumor medicine.