X-Ray-Triggered CO-Release from Gold Nanocluster: All-in-one Nanoplatforms for Cancer Targeted Gas and Radio Synergistic Therapy.

Glycolysis-dominant metabolic pathway in cancer cells can promote their therapeutic resistance against radiotherapy (RT). Carbon monoxide (CO) as a glycolysis inhibitor can enhance the efficiency of RT. Herein, we developed an X-ray responsive CO-releasing nanocomposite (HA@AuNC@CO) based on strong host-guest interactions between the radiosensitizer and CO donor for enhanced RT. The encapsulated gold nanoclusters (CD-AuNCs) could effectively generate cytotoxic reactive oxygen species (ROS) under X-ray radiation, which not only directly inactivate cancer cells but also induce in situ CO gas generation from adamantane modified metal carbonyl (Ada-CO) for glycolysis inhibition. Both in vitro and in vivo results demonstrated that HA@AuNC@CO exhibited active targeting towards CD44 overexpressed cancer cells, along with excellent inhibition of glycolysis and efficient RT against cancer. This study offers a new strategy for the combination of gas therapy and RT in tumor treatment. This article is protected by copyright. All rights reserved.