Computed Tomography Imaging Guided Microenvironment-Responsive Ir@WO Dual-Catalytic Nanoreactor for Selective Radiosensitization.

Radiotherapy (RT) is often administered, either alone or in combination with other therapies, for most malignancies. However, the degree of tumor oxygenation, damage to adjacent healthy tissues, and inaccurate guidance remain issues that result in discontinuation or failure of RT. Here, a multifunctional therapeutic platform based on Ir@WO is developed which simultaneously addresses these critical issues above for precision radiosensitization. Ir@WO nanoreactors exhibit strong absorption of X-ray, acting as radiosensitizers. Moreover, ultrasmall Ir enzyme-mimic nanocrystals (NCs) are decorated onto the surface of the nanoreactor, where NCs have catalyst-like activity and are sensitive to HO in the tumor microenvironment (TME) under near infrared-II (NIR-II) light stimulation. They efficiently catalyze the conversion of HO to O, thereby ameliorating hypoxia, inhibiting the expression of HIF-1α, and enhancing RT-induced DNA damage in cancerous tissue, further improving the efficiency of RT. Additionally, in response to high HO levels in TME, the Ir@WO nanoreactor also exerts peroxidase-like activity, boosting exogenous ROS, which increases oxidative damage and enhances ROS-dependent death signaling. Furthermore, Ir@WO can serve as a high-quality computed tomography contrast agent due to its high X-ray attenuation coefficient and generation of pronounced tumor-tissue contrast. This report highlights the potential of advanced health materials to enhance precision therapeutic modalities.