Radiation‐Triggered Catalytic Decaging in Living Mice

ABSTRACT

Precise spatiotemporal control over chemical reactivity in living systems remains a formidable challenge, especially within deep tissues where light‐based methods suffer from limited penetration. Here, we present a γ‐radiation‐mediated catalytic decaging (γ‐RCD) strategy that harnesses hydrated electrons generated during low‐dose γ‐radiation to activate palladium catalysts, thereby initiating a catalytic cycle for the efficient release of functional molecules. Unlike conventional radiation‐triggered decaging, which relies on primary radiolytic species and suffers from inherently low yields, γ‐RCD achieves catalytic amplification, significantly enhancing radiochemical efficiency with G ‐values up to 25.8‐surpassing existing radiation chemistries by at least 20‐fold. We demonstrate the versatility of γ‐RCD in remotely activating fluorophores, as well as prodrugs with minimal radiation input. The selective activation of caged bioactive compounds in tumor‐bearing mice leads to potent antitumor effects and the translational potential of the γ‐RCD strategy. By integrating catalytic amplification with clinically relevant γ‐radiation, γ‐RCD opens a new avenue for precision medicine, functional biomaterials, and radiation‐responsive therapeutics.