Co-delivery of CO/H₂ gases for synergistic radiosensitization and intestinal protection in peritoneal metastases therapy.

Abstract

The combination of radiosensitizing carbon monoxide (CO) and radioprotective hydrogen (H₂) holds significant potential in whole abdominal radiotherapy for the treatment of peritoneal metastases of colon cancer. However, the concurrent and controlled release of dual gases poses substantial challenges because of their inherently unstable and uncoordinated release profiles. Here, we develop a novel dual gas nanosystem by encapsulating unstable iron carbonyl (FeCO) and ammonium borane (AB) within a stable silica matrix, enabling the on-demand release of CO and H₂. This dual-gas nanosystem prevents premature release in acidic gastric environments and enables the sustained release (>50 h) of H₂ in the intestinal tract, effectively providing protection against radiotherapy-induced intestinal injury. Notably, upon X-ray irradiation of the tumor site, the nanosystem rapidly releases CO to increase radiosensitivity while concurrently releasing H₂ to repair radiation-induced intestinal damage. This spatiotemporal control over the release of CO and H₂ offers a promising therapeutic strategy for efficiently treating peritoneal metastases while reducing the adverse effects associated with radiation therapy.