Radio-Activated Selenium-Doped Janus Ag/Ag2SexSy Nanoparticles for Precise Cancer NIR-II Fluorescence Imaging and Radiosensitization Therapy.

The efficacy of radiotherapy (RT) is often limited by insufficient tumor selectivity and suboptimal therapeutic responses. To overcome these problems, a new kind of selenium-doped Ag/Ag2S Janus nanoparticles (Ag/Ag2SexSy JNPs) is presented as radio-responsive molecular probes for precise tumor imaging and enhanced radiosensitization. By adjusting the selenium precursor input, heterojunction nanoparticles with tunable doping ratios are synthesized, optimizing X-ray absorption and energy storage properties. Upon X-ray irradiation, the Ag/Ag2SexSy JNPs interact with overexpressed hydrogen peroxide (H2O2) in tumor cells, generating highly toxic hydroxyl radicals (·OH), which effectively induce tumor cell apoptosis. Additionally, Selenium incorporation improves electron-hole pair separation efficiency and enhances the photocurrent response, promoting increased electron transfer and ·OH generation, thus amplifying reactive oxygen species (ROS) production and enhancing radiosensitization. Furthermore, the fluorescence "OFF-ON" mechanism, triggered by H2O2-induced etching of silver allows real-time monitoring of H2O2 levels via the second near-infrared window (NIR-II) fluorescence (FL) imaging "Turn On", which delineates tumor boundaries for precise RT and reduce side effects to normal tissue. This dual-functional platform not only enables real-time tracking but also enhances therapeutic outcomes, offering a promising approach to precision cancer treatment.