Radiation-Triggered Catalytic Decaging in Living Mice

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.