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

Abstract 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, 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 is developed. The encapsulated gold nanoclusters (CD‐AuNCs) can 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 demonstrate that HA@AuNC@CO exhibits active targeting toward 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.