Noncontact Environmental Radiation Sensitization via Photoresponse Processes Mediated by Nanostructured Ru-Based Photosensitizers with Near-Infrared Responsiveness

Ovarian cancer is notorious for peritoneal dissemination and chemoresistance caused by its REDOX homeostasis. Ruthenium-based photosensitizers that destroy the REDOX homeostasis in tumor cells by oxidizing NADH and generating ROS can respond only to blue-green light with poor tissue penetration, thus limiting further clinical applications. Thus, a Ru-based nanoplatform (MR@Au) integrating Mn structural sites and <i>in situ</i>-grown single-atom Au clusters was developed to overcome the limited tissue penetration depth of light sources in the photocatalytic process mediated by Ru-based photosensitizers. This system is engineered for NIR-II photoacoustic imaging-guided redox homeostasis disruption and nonhigh-<i>Z</i>-element-dependent radiosensitization strategy. The localized surface plasmon resonance (LSPR) effect induced by monodispersed Au single-atom clusters endows MR@Au with full-spectrum absorption spanning 500-800 nm, enabling efficient responsiveness to NIR irradiation. The discrete atomic distribution of Au clusters facilitates rapid biodegradation and renal clearance─a critical advantage absent in conventional high-Z-element-based radiosensitizers. MR@Au, engineered to enable deep-tissue photodynamic activation and ensure rapid metabolic clearance, proposes a clinically translatable radiosensitization strategy for drug-resistant malignancies while it redefines the design paradigm for small-molecule photosensitizer-based therapy.