X-ray-controllable release of carbon monoxide potentiates radiotherapy by ultrastable hybrid nanoreservoirs

• Published in: Biomaterials 2023-11, Vol.302, p.122313-122313, Article 122313
• Main Authors: Lu, Junna, Chen, Fangman, Xie, Xiaochun, Wu, Ziping, Chen, Yinglu, Zhang, Yidan, Fang, Hui, Ruan, Feixia, Shao, Dan, Wang, Zheng, Pei, Renjun
• Format: Article
• Language: English
• Subjects: biocompatible materials; Carbon monoxide; cell death; colon; Fenton-like reaction; metastasis; Nanoreservoir; nanotechnology; neoplasms; Peritoneal carcinomatosis; porous media; Radiotherapy; silica; X-radiation
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2023.122313

Carbon monoxide (CO) exhibits unique abilities in sensitizing cancer radiotherapy (RT). However, the development of a highly stable CO-delivery nanosystem with sustained CO release in tumor tissues and the prevention of CO leakage into normal tissues remains a challenge. Herein, an organic-inorganic hybrid strategy is proposed to create ultrastable CO nanoreservoirs by locking an unstable iron carbonyl (FeCO) prodrug in a stable mesoporous silica matrix. Different from traditional FeCO-loading nanoplatforms, FeCO-bridged nanoreservoirs not only tethered labile FeCO in the framework to prevent unwanted FeCO leakage, but also achieved sustained CO release in response to X-ray and endogenous H2O2. Importantly, FeCO-bridged nanoreservoirs exhibited the sequential release of CO and Fe2+, thereby performing highly efficient chemodynamic therapy. Such a powerful combination of RT, gas therapy, and chemodynamic therapy boosts robust immunogenic cell death, thus enabling the elimination of deeply metastatic colon tumors with minimal side effects. The proposed organic-inorganic hybrid strategy opens a new window for the development of stable nanoreservoirs for the on-demand delivery of unstable gases and provides a feasible approach for the sequential release of CO and metal ions from metal carbonyl complexes.